Vascular surveillance by haptotactic blood platelets in inflammation and infection

Nicolai, Leo; Schiefelbein, Karin; Lipsky, Silvia; Leunig, Alexander; Hoffknecht, Marie; Pekayvaz, Kami; Raude, Ben; Marx, Charlotte; Ehrlich, Andreas; Pircher, Joachim; Zhang, Zhe; Saleh, Inas; Marel, Anna-Kristina; Lof, Achim; Petzold, Tobias; Lorenz, Michael; Stark, Konstantin; Pick, Robert; Rosenberger, Gerhild; Weckbach, Ludwig; Uhl, Bernd; Xia, Sheng; Reichel, Christoph Andreas; Walzog, Barbara; Schulz, Christian; Zheden, Vanessa; Bender, Markus; Li, Rong; Massberg, Steffen und Gaertner, Florian (2020): Vascular surveillance by haptotactic blood platelets in inflammation and infection. In: Nature Communications, Bd. 11, Nr. 1, 5778

Abstract

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets. Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 833440
• EU-Projekte: Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 833440: IMMUNOTHROMBOSIS - Cross-talk between platelets and immunity - implications for host homeostasis and defense
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2041-1723
• Sprache: Englisch