Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion

Pruenster, Monika, Kurz, Angela R. M., Chung, Kyoung-Jin, Cao-Ehlker, Xiao, Bieber, Stephanie, Nussbaum, Claudia F., Bierschenk, Susanne, Eggersmann, Tanja K., Rohwedder, Ina, Heinig, Kristina, Immler, Roland, Moser, Markus, Koedel, Uwe, Gran, Sandra, McEver, Rodger P., Vestweber, Dietmar, Verschoor, Admar, Leanderson, Tomas, Chavakis, Triantafyllos, Roth, Johannes, Vogl, Thomas and Sperandio, Markus (2015): Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion. In: Nature Communications, Vol. 6, 6915

Abstract

Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid beta 2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo.

• Item Type: Journal article
• Faculties: Medicine > Institute of Cardiovascular Physiology and Pathophysiology
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2041-1723
• Language: English