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

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

Authors :
Pruenster M
Kurz AR
Chung KJ
Cao-Ehlker X
Bieber S
Nussbaum CF
Bierschenk S
Eggersmann TK
Rohwedder I
Heinig K
Immler R
Moser M
Koedel U
Gran S
McEver RP
Vestweber D
Verschoor A
Leanderson T
Chavakis T
Roth J
Vogl T
Sperandio M
Source :
Nature communications [Nat Commun] 2015 Apr 20; Vol. 6, pp. 6915. Date of Electronic Publication: 2015 Apr 20.
Publication Year :
2015

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 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.

Details

Language :
English
ISSN :
2041-1723
Volume :
6
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
25892652
Full Text :
https://doi.org/10.1038/ncomms7915