First Author | Pruenster M | Year | 2015 |
Journal | Nat Commun | Volume | 6 |
Pages | 6915 | PubMed ID | 25892652 |
Mgi Jnum | J:222703 | Mgi Id | MGI:5645408 |
Doi | 10.1038/ncomms7915 | Citation | Pruenster M, et al. (2015) Extracellular MRP8/14 is a regulator of beta2 integrin-dependent neutrophil slow rolling and adhesion. Nat Commun 6:6915 |
abstractText | 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 beta2 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. |