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A role for Syk-kinase in the control of the binding cycle of the β2 integrins (CD11/CD18) in human polymorphonuclear neutrophils

By Thomas Willeke, Jürgen Schymeinsky, Peggy Prange, Stefan Zahler and Barbara Walzog

Abstract

A fine control of β2 integrin (CD11/CD18)-mediated firm adhesion of human neutrophils to the endothelial cell monolayer is required to allow ordered emigration. To elucidate the molecular mechanisms that control this process, intracellular protein tyrosine signaling subsequent to β2 integrin-mediated ligand binding was studied by immunoprecipitation and Western blotting techniques. The 72-kDa Syk-kinase, which was tyrosine-phosphorylated upon adhesion, was found to coprecipitate with CD18, the β-subunit of the β2 integrins. Moreover, inhibition of Syk-kinase by piceatannol enhanced adhesion and spreading but diminished N-formyl-Met-Leu-Phe-induced chemotactic migration. The enhancement of adhesiveness was associated with integrin clustering, which results in increased integrin avidity. In contrast, piceatannol had no effect on the surface expression or on the affinity of β2 integrins. Altogether, this suggests that Syk-kinase controls alternation of β2 integrin-mediated ligand binding with integrin detachment.

Topics: Chemie und Pharmazie, ddc:540
Year: 2003
DOI identifier: 10.1189/jlb.0102016
OAI identifier: oai:epub.ub.uni-muenchen.de:14399
Provided by: Open Access LMU

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