Interaction between integrin α9β1 and vascular cell adhesion molecule-1 (VCAM-1) inhibits neutrophil apoptosis

Abstract

According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-β and provided an additive, increased delay in apoptosis when given in combination with IFN-β. VCAM-1 delivered its antiapoptotic effect through binding the integrin α9β1. The α9β 1 signaling pathway shares significant features with the IFN-β survival signaling pathway, requiring PI3 kinase, NF-κB activation, as well as de novo protein synthesis, but the kinetics of NF-κB activation by VCAM-1 were slower and more sustained compared with IFN-β. This study demonstrates a novel functional role for α9β1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues.

Publication DOI: https://doi.org/10.1182/blood-2005-07-2692
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences
Additional Information: © 2006 by The American Society of Hematology
Uncontrolled Keywords: Immunology,Biochemistry,Hematology,Cell Biology
Publication ISSN: 1528-0020
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://ashpubl ... 21-and-vascular (Publisher URL)
PURE Output Type: Article
Published Date: 2006-02-01
Authors: Ross, Ewan A. (ORCID Profile 0000-0001-5733-9361)
Douglas, Mike R.
See, Heng Wong
Ross, Emma J.
Curnow, S. John
Nash, Gerard B.
Rainger, Ed
Scheel-Toellner, Dagmar
Lord, Janet M.
Salmon, Mike
Buckley, Christopher D.

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