Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

Maas, Sanne L.; Soehnlein, Oliver und Viola, Joana R. (27. November 2018): Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta. In: Frontiers in Immunology, Bd. 9, Nr. 2739: S. 1-24

Abstract

Immune responses are dependent on the recruitment of leukocytes to the site of inflammation. The classical leukocyte recruitment cascade, consisting of capture, rolling, arrest, adhesion, crawling, and transendothelial migration, is thoroughly studied but mostly in model systems, such as the cremasteric microcirculation. This cascade paradigm, which is widely accepted, might be applicable to many tissues, however recruitment mechanisms might substantially vary in different organs. Over the last decade, several studies shed light on organ-specific mechanisms of leukocyte recruitment. An improved awareness of this matter opens new therapeutic windows and allows targeting inflammation in a tissue-specific manner. The aim of this review is to summarize the current understanding of the leukocyte recruitment in general and how this varies in different organs. In particular we focus on neutrophils, as these are the first circulating leukocytes to reach the site of inflammation. Specifically, the recruitment mechanism in large arteries, as well as vessels in the lungs, liver, and kidney will be addressed.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 675111
• EU-Projekte: Horizon 2020 > Marie Skłodowska Curie Actions > Marie Skłodowska-Curie Innovative Training Networks > 675111: EVOLUTION - European Vascular Interventions and Therapeutic Innovation Network
• Keywords: Neutrophil; recruitment; lung; Liver; Kidney; aorta; inflammation; organ-specific
• Fakultät: Medizin
• Themengebiete: 500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften
• ISSN: 1664-3224
• Sprache: Englisch

Literaturliste

1. Ortega-Gomez A, Perretti M, Soehnlein O. Resolution of inflammation: an integrated view. EMBO Mol Med. (2013) 5:661–74. doi: 10.1002/emmm.201202382

2. Nourshargh S, Alon R. Leukocyte migration into inflamed tissues. Immunity (2014) 41:694–707. doi: 10.1016/j.immuni.2014.10.008

3. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature (2014) 510:92–101. doi: 10.1038/nature13479

4. Kourtzelis I, Mitroulis I, von Renesse J, Hajishengallis G, Chavakis T. From leukocyte recruitment to resolution of inflammation: the cardinal role of integrins. J Leukoc Biol. (2017) 102:677–83. doi: 10.1189/jlb.3MR0117-024R

5. Kadl A, Leitinger N. The role of endothelial cells in the resolution of acute inflammation. Antioxid Redox Signal (2005) 7:1744–54. doi: 10.1089/ars.2005.7.1744

6. Charo IF, Taub R. Anti-inflammatory therapeutics for the treatment of atherosclerosis. Nat Rev Drug Discov. (2011) 10:365–76. doi: 10.1038/nrd3444

7. Tabas I, Glass CK. Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science (2013) 339:166–72. doi: 10.1126/science.1230720

8. Rossaint J, Zarbock A. Tissue-specific neutrophil recruitment into the lung, liver, and kidney. J Innate Immun. (2013) 5:348–57. doi: 10.1159/000345943

9. Drechsler M, Megens RT, van Zandvoort M, Weber C, Soehnlein O. Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation (2010) 122:1837–45. doi: 10.1161/CIRCULATIONAHA.110.961714

10. Ortega-Gomez A, Salvermoser M, Rossaint J, Pick R, Brauner J, Lemnitzer P, et al. Cathepsin G controls arterial but not venular myeloid cell recruitment. Circulation (2016) 134:1176–88. doi: 10.1161/CIRCULATIONAHA.116.024790

11. Zahr A, Alcaide P, Yang J, Jones A, Gregory M, dela Paz NG, et al. Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions. Nat Commun. (2016) 7:10363. doi: 10.1038/ncomms10363

12. Marki A, Esko JD, Pries AR, Ley K. Role of the endothelial surface layer in neutrophil recruitment. J Leukoc Biol. (2015) 98:503–15. doi: 10.1189/jlb.3MR0115-011R

13. Hickey MJ, Westhorpe CL. Imaging inflammatory leukocyte recruitment in kidney, lung and liver–challenges to the multi-step paradigm. Immunol Cell Biol. (2013) 91:281–9. doi: 10.1038/icb.2012.83

14. Jung U, Ley K. Regulation of E-selectin, P-selectin, and intercellular adhesion molecule 1 expression in mouse cremaster muscle vasculature. Microcirculation (1997) 4:311–9. doi: 10.3109/10739689709146794

15. Muller WA. Getting leukocytes to the site of inflammation. Vet Pathol. (2013) 50:7–22. doi: 10.1177/0300985812469883

16. Condliffe AM, Kitchen E, Chilvers ER. Neutrophil priming: pathophysiological consequences and underlying mechanisms. Clin Sci. (1998) 94:461–71.

17. Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol. (2010) 31:318–24. doi: 10.1016/j.it.2010.05.006

18. Fossati G, Mazzucchelli I, Gritti D, Ricevuti G, Edwards SW, Moulding DA, et al. In vitro effects of GM-CSF on mature peripheral blood neutrophils. Int J Mol Med. (1998) 1:943–51.

19. Potera RM, Jensen MJ, Hilkin BM, South GK, Hook JS, Gross EA, et al. Neutrophil azurophilic granule exocytosis is primed by TNF-alpha and partially regulated by NADPH oxidase. Innate Immun. (2016) 22:635–46. doi: 10.1177/1753425916668980

20. McLeish KR, Merchant ML, Creed TM, Tandon S, Barati MT, Uriarte SM, et al. Frontline Science: Tumor necrosis factor-alpha stimulation and priming of human neutrophil granule exocytosis. J Leukoc Biol. (2017) 102:19–29. doi: 10.1189/jlb.3HI0716-293RR

21. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. (2012) 30:459–89. doi: 10.1146/annurev-immunol-020711-074942

22. Didsbury JR, Uhing RJ, Tomhave E, Gerard C, Gerard N, Snyderman R. Receptor class desensitization of leukocyte chemoattractant receptors. Proc Natl Acad Sci USA. (1991) 88:11564–8.

23. Claing A, Laporte SA, Caron MG, Lefkowitz RJ. Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and beta-arrestin proteins. Prog Neurobiol. (2002) 66:61–79. doi: 10.1016/S0301-0082(01)00023-5

24. Hong CW. Current understanding in neutrophil differentiation and heterogeneity. Immune Netw. (2017) 17:298–306. doi: 10.4110/in.2017.17.5.298

25. Miralda I, Uriarte SM, McLeish KR. Multiple phenotypic changes define neutrophil priming. Front Cell Infect Microbiol. (2017) 7:217. doi: 10.3389/fcimb.2017.00217

26. Doerfler ME, Danner RL, Shelhamer JH, Parrillo JE. Bacterial lipopolysaccharides prime human neutrophils for enhanced production of leukotriene B4. J Clin Invest. (1989) 83:970–7. doi: 10.1172/JCI113983

27. Swain SD, Rohn TT, Quinn MT. Neutrophil priming in host defense: role of oxidants as priming agents. Antioxid Redox Signal (2002) 4:69–83. doi: 10.1089/152308602753625870

28. Guthrie LA, McPhail LC, Henson PM, Johnston RB Jr. Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipopolysaccharide. Evidence for increased activity of the superoxideproducing enzyme. J Exp Med. (1984) 160:1656–71.

29. Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. (2014) 9:181–218. doi: 10.1146/annurev-pathol-020712-164023

30. Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. (2007) 7:803–15. doi: 10.1038/nri2171

31. Tedder TF, Steeber DA, Chen A, Engel P. The selectins: vascular adhesion molecules. FASEB J. (1995) 9:866–73.

32. Schweitzer KM, Drager AM, van der Valk P, Thijsen SF, Zevenbergen A, Theijsmeijer AP, et al. Constitutive expression of E-selectin and vascular cell adhesion molecule-1 on endothelial cells of hematopoietic tissues. Am J Pathol. (1996) 148:165–75.

33. Weninger W, Ulfman LH, Cheng G, Souchkova N, Quackenbush EJ, Lowe JB, et al. Specialized contributions by alpha(1,3)-fucosyltransferase-IV and FucT-VII during leukocyte rolling in dermal microvessels. Immunity (2000) 12:665–76. doi: 10.1016/S1074-7613(00)80217-4

34. Chong BF, Murphy JE, Kupper TS, Fuhlbrigge RC. E-selectin, thymusand activation-regulated chemokine/CCL17, and intercellular adhesion molecule-1 are constitutively coexpressed in dermal microvessels: a foundation for a cutaneous immunosurveillance system. J Immunol. (2004) 172:1575–81. doi: 10.4049/jimmunol.172.3.1575 Frontiers in Immunology | www.frontiersin.org 18 November 2018 | Volume 9 | Article 2739 Maas et al. Organ-Specific Transendothelial Neutrophil Migration

35. Mazo IB, Gutierrez-Ramos JC, Frenette PS, Hynes RO, Wagner DD, von Andrian UH. Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. J Exp Med. (1998) 188:465–74.

36. Moore KL, Patel KD, Bruehl RE, Li F, Johnson DA, Lichenstein HS, et al. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J Cell Biol. (1995) 128:661–71.

37. Hidalgo A, Peired AJ, Wild M, Vestweber D, Frenette PS. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44. Immunity (2007) 26:477–89. doi: 10.1016/j.immuni.2007.03.011

38. Issekutz AC, Issekutz TB. The contribution of LFA-1 (CD11a/CD18) and MAC-1 (CD11b/CD18) to the in vivo migration of polymorphonuclear leucocytes to inflammatory reactions in the rat. Immunology (1992) 76:655–61.

39. Phillipson M, Kubes P. The neutrophil in vascular inflammation. Nat Med. (2011) 17:1381–90. doi: 10.1038/nm.2514

40. Yago T, Zhang N, Zhao L, Abrams CS, McEver RP. Selectins and chemokines use shared and distinct signals to activate beta2 integrins in neutrophils. Blood Adv. (2018) 2:731–44. doi: 10.1182/bloodadvances.2017015602

41. Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science (2003) 301:1720–5. doi: 10.1126/science.1084174

42. Luo BH, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu Rev Immunol. (2007) 25:619–47. doi: 10.1146/annurev.immunol.25.022106.141618

43. Wegener KL, Partridge AW, Han J, Pickford AR, Liddington RC, Ginsberg MH, et al. Structural basis of integrin activation by talin. Cell (2007) 128:171–

82. doi: 10.1016/j.cell.2006.10.048

44. Vinogradova O, Velyvis A, Velyviene A, Hu B, Haas T, Plow E, et al. A structural mechanism of integrin alpha(IIb)beta(3) “inside-out” activation as regulated by its cytoplasmic face. Cell (2002) 110:587–97. doi: 10.1016/S0092-8674(02)00906-6

45. Lammermann T, Afonso PV, Angermann BR, Wang JM, Kastenmuller W, Parent CA, et al. Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature (2013) 498:371–5. doi: 10.1038/nature12175

46. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. (2007) 7:678–89. doi: 10.1038/nri2156

47. Springer TA. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol. (1995) 57:827–72. doi: 10.1146/annurev.ph.57.030195.004143

48. McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. (2015) 107:331–9. doi: 10.1093/cvr/cvv154

49. Lefort CT, Rossaint J, Moser M, Petrich BG, Zarbock A, Monkley SJ, et al. Distinct roles for talin-1 and kindlin-3 in LFA-1 extension and affinity regulation. Blood (2012) 119:4275–82. doi: 10.1182/blood-2011-08- 373118

50. Morikis VA, Chase S, Wun T, Chaikof EL, Magnani JL, Simon SI. Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inflamed endothelium under shear flow. Blood (2017) 130:2101–10. doi: 10.1182/blood-2017-05-783027

51. Phillipson M, Heit B, Colarusso P, Liu L, Ballantyne CM, Kubes P. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med. (2006) 203:2569–75. doi: 10.1084/jem.20060925

52. Jones DH, Anderson DC, Burr BL, Rudloff HE, Smith CW, Krater SS, et al. Quantitation of intracellular Mac-1 (CD11b/CD18) pools in human neutrophils. J Leukoc Biol. (1988) 44:535–44.

53. Halai K, Whiteford J, Ma B, Nourshargh S, Woodfin A. ICAM-2 facilitates luminal interactions between neutrophils and endothelial cells in vivo. J Cell Sci. (2014) 127(Pt 3):620–9. doi: 10.1242/jcs.137463

54. Foxman EF, Campbell JJ, Butcher EC. Multistep navigation and the combinatorial control of leukocyte chemotaxis. J Cell Biol. (1997) 139:1349–60.

55. Foxman EF, Kunkel EJ, Butcher EC. Integrating conflicting chemotactic signals. The role of memory in leukocyte navigation. J Cell Biol. (1999) 147:577–88.

56. Heit B, Robbins SM, Downey CM, Guan Z, Colarusso P, Miller BJ, et al. PTEN functions to ‘prioritize’ chemotactic cues and prevent ‘distraction’ in migrating neutrophils. Nat Immunol. (2008) 9:743–52. doi: 10.1038/ni.1623

57. Khan AI, Heit B, Andonegui G, Colarusso P, Kubes P. Lipopolysaccharide: a p38 MAPK-dependent disrupter of neutrophil chemotaxis. Microcirculation (2005) 12:421–32. doi: 10.1080/10739680590960368

58. Kim D, Haynes CL. Neutrophil chemotaxis within a competing gradient of chemoattractants. Anal Chem. (2012) 84:6070–8. doi: 10.1021/ac3009548

59. Sadik CD, Kim ND, Luster AD. Neutrophils cascading their way to inflammation. Trends Immunol. (2011) 32:452–60. doi: 10.1016/j.it.2011.06.008

60. Woodfin A, Voisin MB, Beyrau M, Colom B, Caille D, Diapouli FM, et al. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol. (2011) 12:761–9. doi: 10.1038/ni.2062

61. Nottebaum AF, Cagna G, Winderlich M, Gamp AC, Linnepe R, Polaschegg C, et al. VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF. J Exp Med. (2008) 205:2929–45. doi: 10.1084/jem.20080406

62. Shaw SK, Ma S, Kim MB, Rao RM, Hartman CU, Froio RM, et al. Coordinated redistribution of leukocyte LFA-1 and endothelial cell ICAM1 accompany neutrophil transmigration. J Exp Med. (2004) 200:1571–80. doi: 10.1084/jem.20040965

63. Allingham MJ, van Buul JD, Burridge K. ICAM-1-mediated, Src- and Pyk2-dependent vascular endothelial cadherin tyrosine phosphorylation is required for leukocyte transendothelial migration. J Immunol. (2007) 179:4053–64. doi: 10.4049/jimmunol.179.6.4053

64. Orsenigo F, Giampietro C, Ferrari A, Corada M, Galaup A, Sigismund S, et al. Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo. Nat Commun. (2012) 3:1208. doi: 10.1038/ncomms2199

65. Wessel F, Winderlich M, Holm M, Frye M, Rivera-Galdos R, Vockel M, et al. Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE-cadherin. Nat Immunol. (2014) 15:223–30. doi: 10.1038/ni.2824

66. Esser S, Lampugnani MG, Corada M, Dejana E, Risau W. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci. (1998) 111 (Pt 13):1853–65.

67. Andriopoulou P, Navarro P, Zanetti A, Lampugnani MG, Dejana E. Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions. Arterioscler Thromb Vasc Biol. (1999) 19:2286–97.

68. Angelini DJ, Hyun SW, Grigoryev DN, Garg P, Gong P, Singh IS, et al. TNFalpha increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia. Am J Physiol Lung Cell Mol Physiol. (2006) 291:L1232–45. doi: 10.1152/ajplung.00109.2006

69. Mamdouh Z, Kreitzer GE, Muller WA. Leukocyte transmigration requires kinesin-mediated microtubule-dependent membrane trafficking from the lateral border recycling compartment. J Exp Med. (2008) 205:951–66. doi: 10.1084/jem.20072328.

70. Sullivan DP, Muller WA. Neutrophil and monocyte recruitment by PECAM, CD99, and other molecules via the LBRC. Semin Immunopathol. (2014) 36:193–209. doi: 10.1007/s00281-013-0412-6.

71. Yoo SK, Huttenlocher A. Spatiotemporal photolabeling of neutrophil trafficking during inflammation in live zebrafish. J Leukoc Biol. (2011) 89:661–7. doi: 10.1189/jlb.1010567

72. Mathias JR, Perrin BJ, Liu TX, Kanki J, Look AT, Huttenlocher A. Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish. J Leukoc Biol. (2006) 80:1281–8. doi: 10.1189/jlb.0506346

73. Buckley CD, Ross EA, McGettrick HM, Osborne CE, Haworth O, Schmutz C, et al. Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration. J Leukoc Biol. (2006) 79:303–11. doi: 10.1189/jlb.0905496

74. Wang J, Hossain M, Thanabalasuriar A, Gunzer M, Meininger C, Kubes P. Visualizing the function and fate of neutrophils in sterile injury and repair. Science (2017) 358:111–6. doi: 10.1126/science.aam9690

75. Colom B, Bodkin JV, Beyrau M, Woodfin A, Ody C, Rourke C, et al. Leukotriene B4-neutrophil elastase axis drives neutrophil reverse Frontiers in Immunology | www.frontiersin.org 19 N Maas et al. Organ-Specific Transendothelial Neutrophil Migration transendothelial cell migration in vivo. Immunity (2015) 42:1075–86. doi: 10.1016/j.immuni.2015.05.010

76. Elks PM, van Eeden FJ, Dixon G, Wang X, Reyes-Aldasoro CC, Ingham PW, et al. Activation of hypoxia-inducible factor-1alpha (Hif-1alpha) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model. Blood (2011) 118:712–22. doi: 10.1182/blood-2010-12-324186

77. Tauzin S, Starnes TW, Becker FB, Lam PY, Huttenlocher A. Redox and Src family kinase signaling control leukocyte wound attraction and neutrophil reverse migration. J Cell Biol. (2014) 207:589–98. doi: 10.1083/jcb.201408090

78. Powell D, Tauzin S, Hind LE, Deng Q, Beebe DJ, Huttenlocher A. Chemokine signaling and the regulation of bidirectional leukocyte migration in interstitial tissues. Cell Rep. (2017) 19:1572–85. doi: 10.1016/j.celrep.2017.04.078

79. Weber EW, Han F, Tauseef M, Birnbaumer L, Mehta D, Muller WA. TRPC6 is the endothelial calcium channel that regulates leukocyte transendothelial migration during the inflammatory response. J Exp Med. (2015) 212:1883–

99. doi: 10.1084/jem.20150353

80. Huang AJ, Manning JE, Bandak TM, Ratau MC, Hanser KR, Silverstein SC. Endothelial cell cytosolic free calcium regulates neutrophil migration across monolayers of endothelial cells. J Cell Biol. (1993) 120:1371–80.

81. Hixenbaugh EA, Goeckeler ZM, Papaiya NN, Wysolmerski RB, Silverstein SC, Huang AJ. Stimulated neutrophils induce myosin light chain phosphorylation and isometric tension in endothelial cells. Am J Physiol. (1997) 273(2 Pt 2):H981–8. doi: 10.1152/ajpheart.1997.273.2.H981

82. Heemskerk N, Schimmel L, Oort C, van Rijssel J, Yin T, Ma B, et al. F-actinrich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling. Nat Commun. (2016) 7:10493. doi: 10.1038/ncomms10493

83. Schaefer A, Te Riet J, Ritz K, Hoogenboezem M, Anthony EC, Mul FP, et al. Actin-binding proteins differentially regulate endothelial cell stiffness, ICAM-1 function and neutrophil transmigration. J Cell Sci. (2014) 127(Pt 20):4470–82. doi: 10.1242/jcs.154708.

84. Yang L, Froio RM, Sciuto TE, Dvorak AM, Alon R, Luscinskas FW. ICAM-1 regulates neutrophil adhesion and transcellular migration of TNFalpha-activated vascular endothelium under flow. Blood (2005) 106:584–92. doi: 10.1182/blood-2004-12-4942

85. Carman CV, Springer TA. A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol. (2004) 167:377–88. doi: 10.1083/jcb.200404129

86. Mamdouh Z, Mikhailov A, Muller WA. Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment. J Exp Med. (2009) 206:2795–808. doi: 10.1084/jem.20082745

87. Wang S, Voisin MB, Larbi KY, Dangerfield J, Scheiermann C, Tran M, et al. Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med. (2006) 203:1519–32. doi: 10.1084/jem.20051210

88. Stark K, Eckart A, Haidari S, Tirniceriu A, Lorenz M, von Bruhl ML, et al. Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and ’instruct’ them with pattern-recognition and motility programs. Nat Immunol. (2013) 14:41–51. doi: 10.1038/ni.2477

89. Proebstl D, Voisin MB, Woodfin A, Whiteford J, D’Acquisto F, Jones GE, et al. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med. (2012) 209:1219–34. doi: 10.1084/jem.20111622

90. Muller WA. Mechanisms of leukocyte transendothelial migration. Annu Rev Pathol. (2011) 6:323–44. doi: 10.1146/annurev-pathol-011110-130224

91. Nourshargh S, Hordijk PL, Sixt M. Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol. (2010) 11:366–78. doi: 10.1038/nrm2889

92. Voisin MB, Nourshargh S. Neutrophil transmigration: emergence of an adhesive cascade within venular walls. J Innate Immun. (2013) 5:336–47. doi: 10.1159/000346659

93. Vestweber D. Relevance of endothelial junctions in leukocyte extravasation and vascular permeability. Ann N Y Acad Sci. (2012) 1257:184–92. doi: 10.1111/j.1749-6632.2012.06558.x

94. Aird WC. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. (2012) 2:a006429. doi: 10.1101/cshperspect.a006429

95. Passerini AG, Polacek DC, Shi C, Francesco NM, Manduchi E, Grant GR, et al. Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta. Proc Natl Acad Sci USA. (2004) 101:2482–7. doi: 10.1073/pnas.0305938101

96. Zhang J, Burridge KA, Friedman MH. In vivo differences between endothelial transcriptional profiles of coronary and iliac arteries revealed by microarray analysis. Am J Physiol Heart Circ Physiol. (2008) 295:H1556–61. doi: 10.1152/ajpheart.00540.2008

97. Simmons GH, Padilla J, Laughlin MH. Heterogeneity of endothelial cell phenotype within and amongst conduit vessels of the swine vasculature. Exp Physiol. (2012) 97:1074–82. doi: 10.1113/expphysiol.2011.064006

98. Ruoslahti E, Rajotte D. An address system in the vasculature of normal tissues and tumors. Annu Rev Immunol. (2000) 18:813–27. doi: 10.1146/annurev.immunol.18.1.813

99. Simonson AB, Schnitzer JE. Vascular proteomic mapping in vivo. J Thromb Haemost. (2007) 5 (Suppl. 1):183–7. doi: 10.1111/j.1538-7836.2007.02551.x

100. Pasqualini R, Ruoslahti E. Organ targeting in vivo using phage display peptide libraries. Nature (1996) 380:364–6. doi: 10.1038/380364a0

101. Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardo-Vila M, Giordano RJ, et al. Steps toward mapping the human vasculature by phage display. Nat Med. (2002) 8:121–7. doi: 10.1038/nm0202-121

102. Wisse E. An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids. J Ultrastruct Res. (1970) 31:125–50.

103. Scott DW, Patel RP. Endothelial heterogeneity and adhesion molecules N-glycosylation: implications in leukocyte trafficking in inflammation. Glycobiology (2013) 23:622–33. doi: 10.1093/glycob/cwt014

104. Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. (2007) 100:158–73. doi: 10.1161/01.RES.0000255691.76142.4a

105. Minami T, Aird WC. Endothelial cell gene regulation. Trends Cardiovasc Med. (2005) 15:174–84. doi: 10.1016/j.tcm.2005.06.002

106. Marcu R, Choi YJ, Xue J, Fortin CL, Wang Y, Nagao RJ, et al. Human organ-specific endothelial cell heterogeneity. iScience (2018) 4:20–35. doi: 10.1016/j.isci.2018.05.003

107. Nolan DJ, Ginsberg M, Israely E, Palikuqi B, Poulos MG, James D, et al. Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell (2013) 26:204–19. doi: 10.1016/j.devcel.2013.06.017

108. Supajatura V, Ushio H, Nakao A, Akira S, Okumura K, Ra C, et al. Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J Clin Invest. (2002) 109:1351–9. doi: 10.1172/JCI14704

109. Enoksson M, Lyberg K, Moller-Westerberg C, Fallon PG, Nilsson G, Lunderius-Andersson C. Mast cells as sensors of cell injury through IL-33 recognition. J Immunol. (2011) 186:2523–8. doi: 10.4049/jimmunol.1003383

110. Abraham SN, St John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. (2010) 10:440–52. doi: 10.1038/nri2782

111. De Filippo K, Dudeck A, Hasenberg M, Nye E, van Rooijen N, Hartmann K, et al. Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood (2013) 121:4930–7. doi: 10.1182/blood-2013-02-486217

112. Cheng X, Veverka V, Radhakrishnan A, Waters LC, Muskett FW, Morgan SH, et al. Structure and interactions of the human programmed cell death 1 receptor. J Biol Chem. (2013) 288:11771–85. doi: 10.1074/jbc.M112.448126

113. Kritas SK, Saggini A, Varvara G, Murmura G, Caraffa A, Antinolfi P, et al. Impact of mast cells on the skin. Int J Immunopathol Pharmacol. (2013) 26:855–9. doi: 10.1177/039463201302600403

114. Nussbaum C, Bannenberg S, Keul P, Graler MH, Goncalves-de-Albuquerque CF, Korhonen H, et al. Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin. Nat Commun. (2015) 6:6416. doi: 10.1038/ncomms7416

115. Abtin A, Jain R, Mitchell AJ, Roediger B, Brzoska AJ, Tikoo S, et al. Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection. Nat Immunol. (2014) 15:45–53. doi: 10.1038/ni.2769

116. Sumagin R, Sarelius IH. Intercellular adhesion molecule-1 enrichment near tricellular endothelial junctions is preferentially associated with leukocyte transmigration and signals for reorganization of these junctions to accommodate leukocyte passage. J Immunol. (2010) 184:5242–52. doi: 10.4049/jimmunol.0903319 Frontiers in Immunology | www.frontiersin.org 20 November 2018 | Volume 9 | Article 2739 Maas et al. Organ-Specific Transendothelial Neutrophil Migration

117. Hirschi KK, D’Amore PA. Pericytes in the microvasculature. Cardiovasc Res. (1996) 32:687–98.

118. Murfee WL, Skalak TC, Peirce SM. Differential arterial/venous expression of NG2 proteoglycan in perivascular cells along microvessels: identifying a venule-specific phenotype. Microcirculation (2005) 12:151–60. doi: 10.1080/10739680590904955

119. Voisin MB, Probstl D, Nourshargh S. Venular basement membranes ubiquitously express matrix protein low-expression regions: characterization in multiple tissues and remodeling during inflammation. Am J Pathol. (2010) 176:482–95. doi: 10.2353/ajpath.2010.090510

120. Voisin MB, Woodfin A, Nourshargh S. Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo. Arterioscler Thromb Vasc Biol. (2009) 29:1193–9. doi: 10.1161/ATVBAHA.109.187450

121. Mydel P, Shipley JM, Adair-Kirk TL, Kelley DG, Broekelmann TJ, Mecham RP, et al. Neutrophil elastase cleaves laminin-332 (laminin-5) generating peptides that are chemotactic for neutrophils. J Biol Chem. (2008) 283:9513–22. doi: 10.1074/jbc.M706239200

122. Vestweber D. How leukocytes cross the vascular endothelium. Nat Rev Immunol. (2015) 15:692–704. doi: 10.1038/nri3908

123. Murphy DD, Wagner RC. Differential contractile response of cultured microvascular pericytes to vasoactive agents. Microcirculation (1994) 1:121–8.

124. Speyer CL, Steffes CP, Ram JL. Effects of vasoactive mediators on the rat lung pericyte: quantitative analysis of contraction on collagen lattice matrices. Microvasc Res. (1999) 57:134–43. doi: 10.1006/mvre.1998.2134

125. Puls A, Eliopoulos AG, Nobes CD, Bridges T, Young LS, Hall A. Activation of the small GTPase Cdc42 by the inflammatory cytokines TNF(alpha) and IL-1, and by the Epstein-Barr virus transforming protein LMP1. J Cell Sci. (1999) 112 ( Pt 17):2983–92.

126. Givens C, Tzima E. Endothelial mechanosignaling: does one sensor fit all? Antioxid Redox Signal (2016) 25:373–88. doi: 10.1089/ars.2015. 6493

127. McSweeney SR, Warabi E, Siow RC. Nrf2 as an endothelial mechanosensitive transcription factor: going with the flow. Hypertension (2016) 67:20–9. doi: 10.1161/HYPERTENSIONAHA.115.06146

128. Sangwung P, Zhou G, Nayak L, Chan ER, Kumar S, Kang DW, et al. KLF2 and KLF4 control endothelial identity and vascular integrity. JCI Insight (2017) 2:e91700. doi: 10.1172/jci.insight.91700

129. Doddaballapur A, Michalik KM, Manavski Y, Lucas T, Houtkooper RH, You X, et al. Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3. Arterioscler Thromb Vasc Biol. (2015) 35:137–45. doi: 10.1161/ATVBAHA.114.304277

130. Fledderus JO, Boon RA, Volger OL, Hurttila H, Yla-Herttuala S, Pannekoek H, et al. KLF2 primes the antioxidant transcription factor Nrf2 for activation in endothelial cells. Arterioscler Thromb Vasc Biol. (2008) 28:1339–46. doi: 10.1161/ATVBAHA.108.165811

131. Heo KS, Fujiwara K, Abe J. Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Circ J. (2011) 75:2722–30. doi: 10.1253/circj.CJ-11-1124

132. Heo KS, Lee H, Nigro P, Thomas T, Le NT, Chang E, et al. PKCzeta mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. J Cell Biol. (2011) 193:867–84. doi: 10.1083/jcb. 201010051

133. Yao Y, Rabodzey A, Dewey CF, Jr. Glycocalyx modulates the motility and proliferative response of vascular endothelium to fluid shear stress. Am J Physiol Heart Circ Physiol. (2007) 293:H1023–30. doi: 10.1152/ajpheart.00162.2007

134. Petzold T, Orr AW, Hahn C, Jhaveri KA, Parsons JT, Schwartz MA. Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells. Am J Physiol Cell Physiol. (2009) 297:C814–22. doi: 10.1152/ajpcell.00226.2009

135. Liu Y, Collins C, Kiosses WB, Murray AM, Joshi M, Shepherd TR, et al. A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. J Cell Biol. (2013) 201:863–73. doi: 10.1083/jcb.201207115

136. Douglas G, Bendall JK, Crabtree MJ, Tatham AL, Carter EE, Hale AB, et al. Endothelial-specific Nox2 overexpression increases vascular superoxide and macrophage recruitment in ApoE(-)/(-) mice. Cardiovasc Res. (2012) 94:20–9. doi: 10.1093/cvr/cvs026

137. Nam D, Ni CW, Rezvan A, Suo J, Budzyn K, Llanos A, et al. Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis. Am J Physiol Heart Circ Physiol. (2009) 297:H1535–43. doi: 10.1152/ajpheart.00510.2009

138. Wang HQ, Bai L, Shen BR, Yan ZQ, Jiang ZL. Coculture with endothelial cells enhances vascular smooth muscle cell adhesion and spreading via activation of beta1-integrin and phosphatidylinositol 3-kinase/Akt. Eur J Cell Biol. (2007) 86:51–62. doi: 10.1016/j.ejcb.2006.09.001

139. Wang W. Change in properties of the glycocalyx affects the shear rate and stress distribution on endothelial cells. J Biomech Eng. (2007) 129:324–9. doi: 10.1115/1.2720909

140. Atherton A, Born GV. Relationship between the velocity of rolling granulocytes and that of the blood flow in venules. J Physiol. (1973) 233:157–65.

141. Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell (1991) 65:859–73.

142. Soehnlein O. Decision shaping neutrophil-platelet interplay in inflammation: from physiology to intervention. Eur J Clin Invest. (2018) 48:e12871. doi: 10.1111/eci.12871

143. Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, et al. Neutrophils scan for activated platelets to initiate inflammation. Science (2014) 346:1234–8. doi: 10.1126/science.1256478

144. Deppermann C, Kubes P. Start a fire, kill the bug: the role of platelets in inflammation and infection. Innate Immun. (2018) 24:335–48. doi: 10.1177/1753425918789255

145. Slaba I, Wang J, Kolaczkowska E, McDonald B, Lee WY, Kubes P. Imaging the dynamic platelet-neutrophil response in sterile liver injury and repair in mice. Hepatology (2015) 62:1593–605. doi: 10.1002/hep.28003

146. Weber C, Springer TA. Neutrophil accumulation on activated, surfaceadherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor. J Clin Invest. (1997) 100:2085–93. doi: 10.1172/JCI119742

147. Bennett JS. Structure and function of the platelet integrin alphaIIbbeta3. J Clin Invest. (2005) 115:3363–9. doi: 10.1172/JCI26989

148. Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res. (2007) 100:1673–85. doi: 10.1161/01.RES.0000267878.97021.ab

149. Simon DI, Chen Z, Xu H, Li CQ, Dong J, McIntire LV, et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med. (2000) 192:193–204. doi: 10.1084/jem.192.2.193

150. Diacovo TG, deFougerolles AR, Bainton DF, Springer TA. A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. J Clin Invest. (1994) 94:1243–51. doi: 10.1172/JCI117442

151. Ostermann G, Weber KS, Zernecke A, Schroder A, Weber C. JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nat Immunol. (2002) 3:151–8. doi: 10.1038/ni755

152. Vanichakarn P, Blair P, Wu C, Freedman JE, Chakrabarti S. Neutrophil CD40 enhances platelet-mediated inflammation. Thromb Res. (2008) 122:346–58. doi: 10.1016/j.thromres.2007.12.019

153. Rainger EG, Chimen M, Harrison MJ, Yates CM, Harrison P, Watson SP, et al. The role of platelets in the recruitment of leukocytes during vascular disease. Platelets (2015) 26:507–20. doi: 10.3109/09537104.2015.1064881

154. Burkhart JM, Vaudel M, Gambaryan S, Radau S, Walter U, Martens L, et al. The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood (2012) 120:e73–82. doi: 10.1182/blood-2012-04-416594

155. von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res. (2007) 100:27–40. doi: 10.1161/01.RES.0000252802.25497.b7

156. Rossaint J, Herter JM, Van Aken H, Napirei M, Doring Y, Weber C, et al. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood (2014) 123:2573–84. doi: 10.1182/blood-2013-07-516484

157. Hartwig H, Drechsler M, Lievens D, Kramp B, von Hundelshausen P, Lutgens E, et al. Platelet-derived PF4 reduces neutrophil apoptosis following arterial occlusion. Thromb Haemost. (2014) 111:562–4. doi: 10.1160/TH13-08-0699 Frontiers in Immunology | www.frontiersin.org 21 November 2018 | Volume 9 | Article 2739 Maas et al. Organ-Specific Transendothelial Neutrophil Migration

158. Gawaz M, Brand K, Dickfeld T, Pogatsa-Murray G, Page S, Bogner C, et al. Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis. Atherosclerosis (2000) 148:75–

85. doi: 10.1016/S0021-9150(99)00241-5

159. Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest. (2005) 115:3378–84. doi: 10.1172/JCI27196

160. Herzog BH, Fu J, Wilson SJ, Hess PR, Sen A, McDaniel JM, et al. Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2. Nature (2013) 502:105–9. doi: 10.1038/nature12501

161. Duerschmied D, Suidan GL, Demers M, Herr N, Carbo C, Brill A, et al. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice. Blood (2013) 121:1008–15. doi: 10.1182/blood-2012-06-437392

162. Campbell EL, Bruyninckx WJ, Kelly CJ, Glover LE, McNamee EN, Bowers BE, et al. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation. Immunity (2014) 40:66–77. doi: 10.1016/j.immuni.2013.11.020

163. Semenza GL. Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (2004) 19:176–82. doi: 10.1152/physiol.00001.2004

164. Scholz CC, Cavadas MA, Tambuwala MM, Hams E, Rodriguez J, von Kriegsheim A, et al. Regulation of IL-1beta-induced NF-kappaB by hydroxylases links key hypoxic and inflammatory signaling pathways. Proc Natl Acad Sci USA. (2013) 110:18490–5. doi: 10.1073/pnas.13097 18110

165. Kong T, Eltzschig HK, Karhausen J, Colgan SP, Shelley CS. Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of beta2 integrin gene expression. Proc Natl Acad Sci USA. (2004) 101:10440–5. doi: 10.1073/pnas.0401339101

166. Peyssonnaux C, Datta V, Cramer T, Doedens A, Theodorakis EA, Gallo RL, et al. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J Clin Invest. (2005) 115:1806–15. doi: 10.1172/JCI23865

167. Peyssonnaux C, Cejudo-Martin P, Doedens A, Zinkernagel AS, Johnson RS, Nizet V. Cutting edge: essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J Immunol. (2007) 178:7516–9. doi: 10.4049/jimmunol.178.12.7516

168. Walmsley SR, Print C, Farahi N, Peyssonnaux C, Johnson RS, Cramer T, et al. Hypoxia-induced neutrophil survival is mediated by HIF1alpha-dependent NF-kappaB activity. J Exp Med. (2005) 201:105–15. doi: 10.1084/jem.20040624

169. Rossi AG, Sawatzky DA, Walker A, Ward C, Sheldrake TA, Riley NA, et al. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med. (2006) 12:1056–64. doi: 10.1038/nm1468

170. Walmsley SR, Chilvers ER, Thompson AA, Vaughan K, Marriott HM, Parker LC, et al. Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice. J Clin Invest. (2011) 121:1053–63. doi: 10.1172/JCI43273

171. Chang SS, Weiss CO, Xue QL, Fried LP. Patterns of comorbid inflammatory diseases in frail older women: the Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci. (2010) 65:407–13. doi: 10.1093/gerona/glp181

172. Han E, Lee YH. Non-alcoholic fatty liver disease: the emerging burden in cardiometabolic and renal diseases. Diabetes Metab J. (2017) 41:430–7. doi: 10.4093/dmj.2017.41.6.430

173. Woodfin A, Reichel CA, Khandoga A, Corada M, Voisin MB, Scheiermann C, et al. JAM-A mediates neutrophil transmigration in a stimulusspecific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration. Blood (2007) 110:1848–56. doi: 10.1182/blood-2006-09-047431

174. Mizgerd JP, Meek BB, Kutkoski GJ, Bullard DC, Beaudet AL, Doerschuk CM. Selectins and neutrophil traffic: margination and Streptococcus pneumoniae-induced emigration in murine lungs. J Exp Med. (1996) 184:639–45.

175. Mulligan MS, Warner RL, Rittershaus CW, Thomas LJ, Ryan US, Foreman KE, et al. Endothelial targeting and enhanced antiinflammatory effects of complement inhibitors possessing sialyl Lewisx moieties. J Immunol. (1999) 162:4952–9.

176. Mizgerd JP, Kubo H, Kutkoski GJ, Bhagwan SD, Scharffetter-Kochanek K, Beaudet AL, et al. Neutrophil emigration in the skin, lungs, and peritoneum: different requirements for CD11/CD18 revealed by CD18-deficient mice. J Exp Med. (1997) 186:1357–64.

177. Xu J, Gao XP, Ramchandran R, Zhao YY, Vogel SM, Malik AB. Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsisinduced lung inflammation by activating beta2 integrins. Nat Immunol. (2008) 9:880–6. doi: 10.1038/ni.1628

178. Doerschuk CM. The role of CD18-mediated adhesion in neutrophil sequestration induced by infusion of activated plasma in rabbits. Am J Respir Cell Mol Biol. (1992) 7:140–8. doi: 10.1165/ajrcmb/7.2.140

179. Kubo H, Doyle NA, Graham L, Bhagwan SD, Quinlan WM, Doerschuk CM. L- and P-selectin and CD11/CD18 in intracapillary neutrophil sequestration in rabbit lungs. Am J Respir Crit Care Med. (1999) 159:267–74. doi: 10.1164/ajrccm.159.1.9709011

180. Kornerup KN, Salmon GP, Pitchford SC, Liu WL, Page CP. Circulating platelet-neutrophil complexes are important for subsequent neutrophil activation and migration. J Appl Physiol. (2010) 109:758–67. doi: 10.1152/japplphysiol.01086.2009

181. Sarieddine MZ, Scheckenbach KE, Foglia B, Maass K, Garcia I, Kwak BR, et al. Connexin43 modulates neutrophil recruitment to the lung. J Cell Mol Med. (2009) 13:4560–70. doi: 10.1111/j.1582-4934.2008.00654.x

182. Wong J, Johnston B, Lee SS, Bullard DC, Smith CW, Beaudet AL, et al. A minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature. J Clin Invest. (1997) 99:2782–90. doi: 10.1172/JCI119468

183. Essani NA, Fisher MA, Simmons CA, Hoover JL, Farhood A, Jaeschke H. Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock. J Leukoc Biol. (1998) 63:288–96.

184. McDonald B, Jenne CN, Zhuo L, Kimata K, Kubes P. Kupffer cells and activation of endothelial TLR4 coordinate neutrophil adhesion within liver sinusoids during endotoxemia. Am J Physiol Gastrointest Liver Physiol. (2013) 305:G797–806. doi: 10.1152/ajpgi.00058.2013

185. Moles A, Murphy L, Wilson CL, Chakraborty JB, Fox C, Park EJ, et al. A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse. J Hepatol. (2014) 60:782–91. doi: 10.1016/j.jhep.2013.12.005

186. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science (2010) 330:362–6. doi: 10.1126/science.1195491

187. Herter JM, Rossaint J, Spieker T, Zarbock A. Adhesion molecules involved in neutrophil recruitment during sepsis-induced acute kidney injury. J Innate Immun. (2014) 6:597–606. doi: 10.1159/000358238

188. Awad AS, Rouse M, Huang L, Vergis AL, Reutershan J, Cathro HP, et al. Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury. Kidney Int. (2009) 75:689–98. doi: 10.1038/ki.2008.648

189. Tanaka S, Tanaka T, Kawakami T, Takano H, Sugahara M, Saito H, et al. Vascular adhesion protein-1 enhances neutrophil infiltration by generation of hydrogen peroxide in renal ischemia/reperfusion injury. Kidney Int. (2017) 92:154–64. doi: 10.1016/j.kint.2017. 01.014

190. Rouschop KM, Roelofs JJ, Claessen N, da Costa Martins P, Zwaginga JJ, Pals ST, et al. Protection against renal ischemia reperfusion injury by CD44 disruption. J Am Soc Nephrol. (2005) 16:2034–43. doi: 10.1681/ASN.2005010054

191. Kuligowski MP, Kitching AR, Hickey MJ. Leukocyte recruitment to the inflamed glomerulus: a critical role for platelet-derived Pselectin in the absence of rolling. J Immunol. (2006) 176:6991–9. doi: 10.4049/jimmunol.176.11.6991

192. Devi S, Li A, Westhorpe CL, Lo CY, Abeynaike LD, Snelgrove SL, et al. Multiphoton imaging reveals a new leukocyte recruitment paradigm in the glomerulus. Nat Med. (2013) 19:107–12. doi: 10.1038/nm.3024

193. Devi S, Kuligowski MP, Kwan RY, Westein E, Jackson SP, Kitching AR, et al. Platelet recruitment to the inflamed glomerulus occurs via an alphaIIbbeta3/GPVI-dependent pathway. Am J Pathol. (2010) 177:1131–42. doi: 10.2353/ajpath.2010.091143 Frontiers in Immunology | www.frontiersin.org 22 November 2018 | Volume 9 | Article 2739 Maas et al. Organ-Specific Transendothelial Neutrophil Migration

194. Sager HB, Dutta P, Dahlman JE, Hulsmans M, Courties G, Sun Y, et al. RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. Sci Transl Med. (2016) 8:342ra80. doi: 10.1126/scitranslmed.aaf1435

195. Collins RG, Velji R, Guevara NV, Hicks MJ, Chan L, Beaud AL P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med. (2000) 191:189–94. doi: 10.1084/jem.191.1.189

196. Johnson RC, Chapman SM, Dong ZM, Ordovas JM, Mayadas TN, Herz J, et al. Absence of P-selectin delays fatty streak formation in mice. J Clin Invest. (1997) 99:1037–43. doi: 10.1172/JCI119231

197. Nageh MF, Sandberg ET, Marotti KR, Lin AH, Melchior EP, Bullard DC, et al. Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol. (1997) 17:1517–20.

198. Schmitt MM, Megens RT, Zernecke A, Bidzhekov K, van den Akker NM, Rademakers T, et al. Endothelial junctional adhesion molecule-a guides monocytes into flow-dependent predilection sites of atherosclerosis. Circulation (2014) 129:66–76. doi: 10.1161/CIRCULATIONAHA.113.004149

199. Winter C, Silvestre-Roig C, Ortega-Gomez A, Lemnitzer P, Poelman H, Schumski A, et al. Chrono-pharmacological targeting of the CCL2- CCR2 axis ameliorates atherosclerosis. Cell Metab. (2018) 28:175–82 e5. doi: 10.1016/j.cmet.2018.05.002

200. Doring Y, Drechsler M, Wantha S, Kemmerich K, Lievens D, Vijayan S, et al. Lack of neutrophil-derived CRAMP reduces atherosclerosis in mice. Circ Res. (2012) 110:1052–6. doi: 10.1161/CIRCRESAHA.112.265868

201. Aird WC. Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res. (2007) 100:174–90. doi: 10.1161/01.RES.0000255690.03436.ae

202. Doerschuk CM. Leukocyte trafficking in alveoli and airway passages. Respir Res. (2000) 1:136–40. doi: 10.1186/rr24

203. Kornmann LM, Zernecke A, Curfs DM, Janssen BJ, Weber C, de Winther MP, et al. Echogenic perfluorohexane-loaded macrophages adhere in vivo to activated vascular endothelium in mice, an explorative study. Cardiovasc Ultrasound. (2015) 13:1. doi: 10.1186/1476-7120-13-1

204. Doerschuk CM, Beyers N, Coxson HO, Wiggs B, Hogg JC. Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung. J Appl Physiol. (1993) 74:3040–5. doi: 10.1152/jappl.1993.74.6.3040

205. Doerschuk CM. Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation (2001) 8:71–88. doi: 10.1111/j.1549-8719.2001.tb00159.x

206. Yipp BG, Kim JH, Lima R, Zbytnuik LD, Petri B, Swanlund N, et al. The lung is a host defense niche for immediate neutrophilmediated vascular protection. Sci Immunol. (2017) 2:eaam8929. doi: 10.1126/sciimmunol.aam8929

207. Moldoveanu B, Otmishi P, Jani P, Walker J, Sarmiento X, Guardiola J, et al. Inflammatory mechanisms in the lung. J Inflamm Res. (2009) 2:1–11. doi: 10.2147/JIR.S4385

208. Dockrell DH, Marriott HM, Prince LR, Ridger VC, Ince PG, Hellewell PG, et al. Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection. J Immunol. (2003) 171:5380–8. doi: 10.4049/jimmunol.171.10.5380

209. Knapp S, Leemans JC, Florquin S, Branger J, Maris NA, Pater J, et al. Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia. Am J Respir Crit Care Med. (2003) 167:171–9. doi: 10.1164/rccm.200207-698OC

210. Wang Z, Rui T, Yang M, Valiyeva F, Kvietys PR. Alveolar macrophages from septic mice promote polymorphonuclear leukocyte transendothelial migration via an endothelial cell Src kinase/NADPH oxidase pathway. J Immunol. (2008) 181:8735–44. doi: 10.4049/jimmunol.181.12.8735

211. Kreisel D, Nava RG, Li W, Zinselmeyer BH, Wang B, Lai J, et al. In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proc Natl Acad Sci USA. (2010) 107:18073–

8. doi: 10.1073/pnas.1008737107

212. Doyle NA, Bhagwan SD, Meek BB, Kutkoski GJ, Steeber DA, Tedder TF, et al. Neutrophil margination, sequestration, and emigration in the lungs of L-selectin-deficient mice. J Clin Invest. (1997) 99:526–33. doi: 10.1172/JCI119189

213. Yao L, Yago T, Shao B, Liu Z, Silasi-Mansat R, Setiadi H, et al. Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice. Blood (2013) 122:3832–42. doi: 10.1182/blood-2012-12-473835

214. Maus UA, Waelsch K, Kuziel WA, Delbeck T, Mack M, Blackwell TS, et al. Monocytes are potent facilitators of alveolar neutrophil emigration during lung inflammation: role of the CCL2-CCR2 axis. J Immunol. (2003) 170:3273–8. doi: 10.4049/jimmunol.170.6.3273

215. Grommes J, Alard JE, Drechsler M, Wantha S, Morgelin M, Kuebler WM, et al. Disruption of platelet-derived chemokine heteromers prevents neutrophil extravasation in acute lung injury. Am J Respir Crit Care Med. (2012) 185:628–36. doi: 10.1164/rccm.201108-1533OC

216. Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. (2007) 13:463–9. doi: 10.1038/nm1565

217. Gregory SH, Sagnimeni AJ, Wing EJ. Bacteria in the bloodstream are trapped in the liver and killed by immigrating neutrophils. J Immunol. (1996) 157:2514–20.

218. Marques PE, Amaral SS, Pires DA, Nogueira LL, Soriani FM, Lima BH, et al. Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure. Hepatology (2012) 56:1971–82. doi: 10.1002/hep.25801

219. Yoon YJ, Chang S, Kim OY, Kang BK, Park J, Lim JH, et al. Threedimensional imaging of hepatic sinusoids in mice using synchrotron radiation micro-computed tomography. PLoS ONE (2013) 8:e68600. doi: 10.1371/journal.pone.0068600

220. McNab G, Reeves JL, Salmi M, Hubscher S, Jalkanen S, Adams DH. Vascular adhesion protein 1 mediates binding of T cells to human hepatic endothelium. Gastroenterology (1996) 110:522–8.

221. Steinhoff G, Behrend M, Schrader B, Duijvestijn AM, Wonigeit K. Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3. Am J Pathol. (1993) 142:481–8.

222. Warren A, Le Couteur DG, Fraser R, Bowen DG, McCaughan GW, Bertolino P. T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells. Hepatology (2006) 44:1182–90. doi: 10.1002/hep.21378

223. Wisse E, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology (1985) 5:683–92.

224. McCuskey RS. The hepatic microvascular system in health and its response to toxicants. Anat Rec. (2008) 291:661–71. doi: 10.1002/ar.20663

225. van Golen RF, van Gulik TM, Heger M. The sterile immune response during hepatic ischemia/reperfusion. Cytokine Growth Factor Rev. (2012) 23:69–84. doi: 10.1016/j.cytogfr.2012.04.006

226. Granger DN. Cell adhesion and migration. II. Leukocyte-endothelial cell adhesion in the digestive system. Am J Physiol. (1997) 273(5 Pt 1):G982–6.

227. Bamboat ZM, Balachandran VP, Ocuin LM, Obaid H, Plitas G, DeMatteo RP. Toll-like receptor 9 inhibition confers protection from liver ischemiareperfusion injury. Hepatology (2010) 51:621–32. doi: 10.1002/hep.23365

228. Marques PE, Oliveira AG, Pereira RV, David BA, Gomides LF, Saraiva AM, et al. Hepatic DNA deposition drives drug-induced liver injury and inflammation in mice. Hepatology (2015) 61:348–60. doi: 10.1002/hep.27216

229. Menezes GB, Lee WY, Zhou H, Waterhouse CC, Cara DC, Kubes P. Selective down-regulation of neutrophil Mac-1 in endotoxemic hepatic microcirculation via IL-10. J Immunol. (2009) 183:7557–68. doi: 10.4049/jimmunol.0901786

230. Jenne CN, Wong CH, Zemp FJ, McDonald B, Rahman MM, Forsyth PA, et al. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps. Cell Host Microbe (2013) 13:169–80. doi: 10.1016/j.chom.2013.01.005

231. McDonald B, Urrutia R, Yipp BG, Jenne CN, Kubes P. Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis. Cell Host Microbe (2012) 12:324–33. doi: 10.1016/j.chom.2012. 06.011

232. Fox-Robichaud A, Kubes P. Molecular mechanisms of tumor necrosis factor alpha-stimulated leukocyte recruitment into the murine hepatic Frontiers in Immunology | www.frontiersin.org 23 November 2018 | Volume 9 | Article 2739 Maas et al. Organ-Specific Transendothelial Neutrophil Migration circulation. Hepatology (2000) 31:1123–7. doi: 10.1053/he.2000. 6961

233. McDonald B, McAvoy EF, Lam F, Gill V, de la Motte C, Savani RC, et al. Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med. (2008) 205:915–27. doi: 10.1084/jem.20071765

234. von Hundelshausen P, Koenen RR, Weber C. Platelet-mediated enhancement of leukocyte adhesion. Microcirculation (2009) 16:84–96. doi: 10.1080/10739680802564787

235. Wong CH, Jenne CN, Petri B, Chrobok NL, Kubes P. Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance. Nat Immunol. (2013) 14:785–92. doi: 10.1038/ni.2631

236. Molema G, Aird WC. Vascular heterogeneity in the kidney. Semin Nephrol. (2012) 32:145–55. doi: 10.1016/j.semnephrol.2012.02.001

237. Aydin S, Signorelli S, Lechleitner T, Joannidis M, Pleban C, Perco P, et al. Influence of microvascular endothelial cells on transcriptional regulation of proximal tubular epithelial cells. Am J Physiol Cell Physiol. (2008) 294:C543–

54. doi: 10.1152/ajpcell.00307.2007

238. Bulger RE, Eknoyan G, Purcell DJ, 2nd, Dobyan DC. Endothelial characteristics of glomerular capillaries in normal, mercuric chlorideinduced, and gentamicin-induced acute renal failure in the rat. J Clin Invest. (1983) 72:128–41.

239. Singh A, Satchell SC, Neal CR, McKenzie EA, Tooke JE, Mathieson PW. Glomerular endothelial glycocalyx constitutes a barrier to protein permeability. J Am Soc Nephrol. (2007) 18:2885–93. doi: 10.1681/ASN.2007010119

240. Haraldsson B, Nystrom J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev. (2008) 88:451–87. doi: 10.1152/physrev.00055.2006

241. Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. (2003) 83:253–307. doi: 10.1152/physrev.00020.2002

242. Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. (2003) 111:707–16. doi: 10.1172/JCI17423

243. Roberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci. (1995) 108 ( Pt 6):2369–79.

244. Meng XM, Nikolic-Paterson DJ, Lan HY. Inflammatory processes in renal fibrosis. Nat Rev Nephrol. (2014) 10:493–503. doi: 10.1038/nrneph.2014.114

245. Herter J, Zarbock A. Integrin Regulation during Leukocyte Recruitment. J Immunol. (2013) 190:4451–7. doi: 10.4049/jimmunol.1203179

246. Azroyan A, Cortez-Retamozo V, Bouley R, Liberman R, Ruan YC, Kiselev E, et al. Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. PLoS ONE (2015) 10:e0121419. doi: 10.1371/journal.pone.0121419

247. Mehrotra P, Collett JA, McKinney SD, Stevens J, Ivancic CM, Basile DP. IL-17 mediates neutrophil infiltration and renal fibrosis following recovery from ischemia reperfusion: compensatory role of natural killer cells in athymic rats. Am J Physiol Renal Physiol. (2017) 312:F385–F97. doi: 10.1152/ajprenal.00462.2016

248. De Vriese AS, Endlich K, Elger M, Lameire NH, Atkins RC, Lan HY, et al. The role of selectins in glomerular leukocyte recruitment in rat antiglomerular basement membrane glomerulonephritis. J Am Soc Nephrol. (1999) 10:2510–7.

249. Janssen U, Ostendorf T, Gaertner S, Eitner F, Hedrich HJ, Assmann KJ, et al. Improved survival and amelioration of nephrotoxic nephritis in intercellular adhesion molecule-1 knockout mice. J Am Soc Nephrol. (1998) 9:1805–14.

250. Tang T, Rosenkranz A, Assmann KJ, Goodman MJ, Gutierrez-Ramos JC, Carroll MC, et al. A role for Mac-1 (CDIIb/CD18) in immune complexstimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complementdependent proteinuria in acute glomerulonephritis. J Exp Med. (1997) 186:1853–63.

251. Wu X, Pippin J, Lefkowith JB. Attenuation of immune-mediated glomerulonephritis with an anti-CD11b monoclonal antibody. Am J Physiol. (1993) 264(4 Pt 2):F715–21. doi: 10.1152/ajprenal.1993.264.4.F715

252. Finsterbusch M, Hall P, Li A, Devi S, Westhorpe CL, Kitching AR, et al. Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus. Proc Natl Acad Sci USA. (2016) 113:E5172–81. doi: 10.1073/pnas.1606253113

253. Herrera MB, Bussolati B, Bruno S, Morando L, Mauriello-Romanazzi G, Sanavio F, et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney Int. (2007) 72:430–41. doi: 10.1038/sj.ki.5002334

254. Pallone TL, Zhang Z, Rhinehart K. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol. (2003) 284:F253–66. doi: 10.1152/ajprenal.00304.2002

255. Gimbrone MA, Jr., Garcia-Cardena G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. (2016) 118:620–36. doi: 10.1161/CIRCRESAHA.115.306301

256. Chevre R, Gonzalez-Granado JM, Megens RT, Sreeramkumar V, SilvestreRoig C, Molina-Sanchez P, et al. High-resolution imaging of intravascular atherogenic inflammation in live mice. Circ Res. (2014) 114:770–9. doi: 10.1161/CIRCRESAHA.114.302590

257. Weber C, Zernecke A, Libby P. The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat Rev Immunol. (2008) 8:802–15. doi: 10.1038/nri2415

258. Soehnlein O. Multiple roles for neutrophils in atherosclerosis. Circ Res. (2012) 110:875–88. doi: 10.1161/CIRCRESAHA.111.257535

259. Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI. The NFkappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA. (2000) 97:9052–7. doi: 10.1073/pnas.97.16.9052

260. Araujo FB, Barbosa DS, Hsin CY, Maranhao RC, Abdalla DS. Evaluation of oxidative stress in patients with hyperlipidemia. Atherosclerosis (1995) 117:61–71.

261. Mazor R, Shurtz-Swirski R, Farah R, Kristal B, Shapiro G, Dorlechter F, et al. Primed polymorphonuclear leukocytes constitute a possible link between inflammation and oxidative stress in hyperlipidemic patients. Atherosclerosis (2008) 197:937–43. doi: 10.1016/j.atherosclerosis.2007.08.014

262. Cheng C, Tempel D, van Haperen R, de Boer HC, Segers D, Huisman M, et al. Shear stress-induced changes in atherosclerotic plaque composition are modulated by chemokines. J Clin Invest. (2007) 117:616–26. doi: 10.1172/JCI28180

263. Springer TA. Adhesion receptors of the immune system. Nature (1990) 346:425–34. doi: 10.1038/346425a0

264. Siminiak T, Flores NA, Sheridan DJ. Neutrophil interactions with endothelium and platelets: possible role in the development of cardiovascular injury. Eur Heart J. (1995) 16:160–70.

265. Badrnya S, Butler LM, Soderberg-Naucler C, Volf I, Assinger A. Platelets directly enhance neutrophil transmigration in response to oxidised low-density lipoprotein. Thromb Haemost. (2012) 108:719–29. doi: 10.1160/TH12-03-0206

266. Soehnlein O, Steffens S, Hidalgo A, Weber C. Neutrophils as protagonists and targets in chronic inflammation. Nat Rev Immunol. (2017) 17:248–61. doi: 10.1038/nri.2017.10

267. Eriksson EE. Intravital microscopy on atherosclerosis in apolipoprotein e-deficient mice establishes microvessels as major entry pathways for leukocytes to advanced lesions. Circulation (2011) 124:2129–38. doi: 10.1161/CIRCULATIONAHA.111. 030627