Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25892652.
- Also identified by DOI 10.1038/ncomms7915 and PMC identifier 4411303.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- CD18 Antigens
- Calgranulin A
- Calgranulin B
- Cell Adhesion
- Leukocyte Rolling
- Neutrophils