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Free keywords:
INFLAMMATION IN-VIVO; E-SELECTIN; LEUKOCYTE-ADHESION; DISEASE-ACTIVITY;
PAQUINIMOD ABR-215757; ENDOTHELIAL-CELLS; PROTEIN COMPLEX; S100
PROTEINS; MRP14; RECEPTOR
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.
