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Granulocyte macrophage‐colony stimulating factor delays neutrophil apoptosis and primes its function through Ia‐type phosphoinositide 3‐kinase
Author(s) -
Yasui Kozo,
Sekiguchi Yukio,
Ichikawa Motoki,
Nagumo Haruo,
Yamazaki Takashi,
Komiyama Atsushi,
Suzuki Harumi
Publication year - 2002
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.72.5.1020
Subject(s) - biology , chemotaxis , phosphoinositide 3 kinase , pi3k/akt/mtor pathway , kinase , protein kinase b , granulocyte , granulocyte macrophage colony stimulating factor , apoptosis , microbiology and biotechnology , superoxide , motility , macrophage , phosphorylation , signal transduction , immunology , receptor , cytokine , biochemistry , in vitro , enzyme
Phosphoinositide 3‐kinases (PI3Ks) constitute a family of lipid kinases that regulate an array of fundamental cellular responses by neutrophils [polymorphonuclear leukocytes (PMN)]. p85α Gene‐disrupted mice were used to help accurately identify the physiological role of the PI3K isoform in PMN activation in the presence of granulocyte macrophage‐colony stimulating factor (GM‐CSF). PMN from the p85α−/− mice showed normal cellular motility, and the quantity of superoxide anion () produced by PMN upon stimulation with formyl‐Met‐Leu‐Phe did not significantly differ between p85α−/− and wild‐type mice under controlled conditions. In p85α−/− mice, the production by PMN was enhanced (primed) by GM‐CSF when stimulated with the chemotactic peptide but to a significantly lesser extent than in wild‐type mice. In addition, no major GM‐CSF‐dependent delay in apoptosis or activation of Akt protein phosphorylation by GM‐CSF was observed in the p85α−/− mice. In terms of targeting strategy, however, the mutation actually expressed a small amount of Ia‐type (p85α‐regulated) PI3K activity (partially abrogated) in the mice. These results demonstrate that Ia‐type PI3K plays a critical role in the enhancement of the GM‐CSF‐modulated function of PMN and in the PI3K/Akt pathway‐dependent delay of PMN apoptosis.