Stimulation of Human Neutrophils by Chemotactic Factors Is Associated with the Activation of Phosphatidylinositol 3-Kinase γ*

Date

2000

Authors

Naccache, P.
Levasseur, S.
Lachance, G.
Chakravarti, S.
Bourgoin, S.
McColl, S.

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Journal of Biological Chemistry, 2000; 275(31):23636-23641

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Paul H. Naccache, Sylvain Levasseur, Genevie, ve Lachance, Sumone Chakravarti, Sylvain G. Bourgoini, and Shaun R. McColl

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Abstract

The activation of human polymorphonuclear neutrophil leukocytes (neutrophils) is associated with an increased synthesis of the highly phosphorylated phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). The aims of the present investigation were to determine whether the newly described, G protein-dependent phosphatidylinositol 3-kinase (PI3K), p110γ, was involved in the responses to chemotactic factors interacting with G protein-coupled receptors. The presence of p110γ in neutrophils was first established both at the protein and the mRNA level. Stimulation of the cells with fMet-Leu-Phe or interleukin-8 increased the PI3K activity in p110γ, but not p85, immunoprecipitates. The time course of this effect (threshold within less than 5 s, maximal activation at 10–15 s) was consistent with that of the generation of PtdIns(3,4,5)P3. Wortmannin, a PI3K inhibitor, abrogated the effects of fMet-Leu-Phe, which were also significantly inhibited by pertussis toxin. Finally, fMet-Leu-Phe also induced a significant translocation of p110γ to a particulate fraction derived from these cells. These data indicate that p110γ represent the major PI3K activated by fMet-Leu-Phe and interleukin-8 at very early time points following the stimulation of human neutrophils.

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© 2000 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. This is an Open Access article under the CC BY license.

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