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Published online before print February 3, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0605350

Received for publication June 29, 2005.
Revised November 2, 2005.
Accepted for publication November 29, 2005.

Article

Chemokine- and adhesion-dependent survival of neutrophils after transmigration through cytokine-stimulated endothelium

Helen M. McGettrick ^*, Janet M. Lord , Ke-Qing Wang , G. Ed Rainger ^*, Christopher D. Buckley ^*, and Gerard B. Nash ^*@

*Centre for Cardiovascular Sciences and MRC Centre for Immune Regulation, The Medical School, The University of Birmingham, United Kingdom

^@ To whom correspondence should be addressed. E-mail: g.nash{at}bham.ac.uk.

	Abstract

We examined the fate of neutrophils following transmigration through an endothelial monolayer cultured on "Transwell" membrane filters. Treatment of human umbilical vein endothelial cells (HUVEC) with increasing doses of tumor necrosis factor- increased the efficiency of transmigration and markedly reduced apoptosis among the transmigrated neutrophils in a dose-dependent manner. Apoptosis was also inhibited after transmigration of neutrophils through HUVEC stimulated with interleukin (IL)-1 but not so effectively after chemotaxis through unstimulated HUVEC driven by IL-8 added below the filter. Inhibition of ₂-integrin binding after transmigration or coating the lower chamber with a nonadhesive polymer (polyhydroxyl-ethyl-methacrylate) abrogated neutrophil survival. Although integrin engagement during migration itself was not essential to inhibit apoptosis, activation of neutrophils through CXC chemokine receptors was necessary. Quite brief exposure to the HUVEC (30-120 min) was effective in reducing subsequent apoptosis, although if coincubation with the HUVEC were prolonged, neutrophil apoptosis was reduced further. Neutralization of granulocyte macrophage-colony stimulating factor inhibited this additional effect. Thus, a complex interplay between migration- and activation-dependent signals and adhesive interaction in tissue may combine to effectively prolong the survival of neutrophils recruited during inflammation.

Key Words: apoptosis • leukocyte trafficking • endothelial cells • adhesion molecules

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