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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.
- 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.
- Subjects :
- Animals
CD18 Antigens genetics
Calgranulin A genetics
Calgranulin B genetics
Gene Expression Regulation
Hyaluronan Receptors genetics
Hyaluronan Receptors metabolism
Inflammation chemically induced
Inflammation metabolism
Macrophages physiology
Male
Mice
Mice, Knockout
Protein Binding
CD18 Antigens metabolism
Calgranulin A metabolism
Calgranulin B metabolism
Cell Adhesion physiology
Leukocyte Rolling physiology
Neutrophils physiology
Subjects
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