Journal of Leukocyte Biology
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A more recent version of this article appeared on February 1, 2004

Published online before print October 23, 2003
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0103038

Received for publication January 23, 2003.
Revised September 19, 2003.
Accepted for publication September 22, 2003.

Article

Aggregation of {beta}2 integrins activates human neutrophils through the I{kappa}B/NF-{kappa}B pathway

Cheol Hyeon Kim , Kyoung-Hee Lee , Choon-Taek Lee , Young Whan Kim , Sung Koo Han , Young-Soo Shim , and Chul-Gyu Yoo @

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine; Clinical Research Institute, Seoul National University Hospital; and Lung Institute, Medical Research Center, Seoul National University, Korea

@ To whom correspondence should be addressed. E-mail: cgyoo{at}snu.ac.kr.


  Abstract

Neutrophils are now considered central to the pathogenesis of most forms of acute lung injury. Neutrophils do not cause damage while suspended in the bloodstream; however, a release of cytotoxic agents occurs when neutrophils are adherent to endothelium, epithelium, or extracellular matrix proteins in the interstitium. Such neutrophil adherence is mediated predominantly through {beta}2 integrins (CD11/CD18) on its surface. This study was undertaken to investigate whether the I{kappa}B/nuclear factor (NF)-{kappa}B cascade is involved in this {beta}2 integrin-mediated activation of human neutrophils. {beta}2 Integrin Mac-1 (CD11b/CD18) aggregation was induced by antibody cross-linking of the integrins on the cell surface. {beta}2 Integrin aggregation induced interleukin-1{beta} and tumor necrosis factor-{alpha} production, which suggests the activation of neutrophils by {beta}2 integrin. I{kappa}B{alpha} was markedly degraded at 1 h, and NF-{kappa}B-DNA-binding activity markedly increased 2 h after {beta}2 integrin aggregation, which activated I{kappa}B kinase activity at 1 h. {beta}2 Integrin-induced cytokine production was suppressed by MG132 or SN50 pretreatment, which blocked the activation of NF-{kappa}B. These findings suggest that the activation of human neutrophils by {beta}2 integrin aggregation is mediated through the activation of the I{kappa}B/NF-{kappa}B pathway.

Key Words: adhesion • acute lung injury • CD11b/CD18 • IL-1{beta} • TNF-{alpha}






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Copyright © 2003 by the Society for Leukocyte Biology.