Pulmonary and Critical Care Medicine Division and.
PubMed | Pulmonary and Critical Care Medicine Division and., David ith Center For Vaccine Biology And Immunology, Netherlands Cancer Institute and University of Rochester
Type: Journal Article | Journal: Blood | Year: 2014
Integrin-mediated migration of neutrophils to infected tissue sites is vital for pathogen clearance and therefore host survival. Although 2 integrins have been shown to mediate neutrophil transendothelial migration during systemic and local inflammation, relatively little information is available regarding neutrophil migration in sepsis beyond the endothelial cell layer. In this study, we report that integrin 31 (VLA-3; CD49c/CD29) is dramatically upregulated on neutrophils isolated from both human septic patients and in mouse models of sepsis. Compared with the 31 (low) granulocytes, 31 (high) cells from septic animals displayed hyperinflammatory phenotypes. Administration of a 31 blocking peptide and conditional deletion of 3 in granulocytes significantly reduced the number of extravasating neutrophils and improved survival in septic mice. In addition, expression of 31 on neutrophils was associated with Toll-like receptor-induced inflammatory responses and cytokine productions. Thus, our results show that 31 is a novel marker of tissue homing and hyperresponsive neutrophil subtypes in sepsis, and blocking of 31 may represent a new therapeutic approach in sepsis treatment.