1. Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion.
- Author
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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, and Sperandio M
- 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
- 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.
- Published
- 2015
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