| First Author | Lerman YV | Year | 2014 |
| Journal | Blood | Volume | 124 |
| Issue | 24 | Pages | 3515-23 |
| PubMed ID | 25278585 | Mgi Jnum | J:220796 |
| Mgi Id | MGI:5636141 | Doi | 10.1182/blood-2014-01-552943 |
| Citation | Lerman YV, et al. (2014) Sepsis lethality via exacerbated tissue infiltration and TLR-induced cytokine production by neutrophils is integrin alpha3beta1-dependent. Blood 124(24):3515-23 |
| abstractText | Integrin-mediated migration of neutrophils to infected tissue sites is vital for pathogen clearance and therefore host survival. Although beta2 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 alpha3beta1 (VLA-3; CD49c/CD29) is dramatically upregulated on neutrophils isolated from both human septic patients and in mouse models of sepsis. Compared with the alpha3beta1 (low) granulocytes, alpha3beta1 (high) cells from septic animals displayed hyperinflammatory phenotypes. Administration of a alpha3beta1 blocking peptide and conditional deletion of alpha3 in granulocytes significantly reduced the number of extravasating neutrophils and improved survival in septic mice. In addition, expression of alpha3beta1 on neutrophils was associated with Toll-like receptor-induced inflammatory responses and cytokine productions. Thus, our results show that alpha3beta1 is a novel marker of tissue homing and hyperresponsive neutrophil subtypes in sepsis, and blocking of alpha3beta1 may represent a new therapeutic approach in sepsis treatment. |
