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Chemokine‐ and adhesion‐dependent survival of neutrophils after transmigration through cytokine‐stimulated endothelium
Author(s) -
McGettrick Helen M.,
Lord Janet M.,
Wang KeQing,
Rainger G. Ed,
Buckley Christopher D.,
Nash Gerard B.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0605350
Subject(s) - umbilical vein , chemokine , biology , apoptosis , chemotaxis , tumor necrosis factor alpha , microbiology and biotechnology , cytokine , integrin , cxc chemokine receptors , interleukin 8 , immunology , human umbilical vein endothelial cell , inflammation , granulocyte , receptor , chemokine receptor , in vitro , biochemistry
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‐α 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)‐1β but not so effectively after chemotaxis through unstimulated HUVEC driven by IL‐8 added below the filter. Inhibition of β 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.