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

نویسندگان

  • Monika Pruenster
  • Angela R M Kurz
  • Kyoung-Jin Chung
  • Xiao Cao-Ehlker
  • Stephanie Bieber
  • Claudia F Nussbaum
  • Susanne Bierschenk
  • Tanja K Eggersmann
  • Ina Rohwedder
  • Kristina Heinig
  • Roland Immler
  • Markus Moser
  • Uwe Koedel
  • Sandra Gran
  • Rodger P McEver
  • Dietmar Vestweber
  • Admar Verschoor
  • Tomas Leanderson
  • Triantafyllos Chavakis
  • Johannes Roth
  • Thomas Vogl
  • Markus Sperandio
چکیده

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 β2 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.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015