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Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation

Science  11 Feb 2000:
Vol. 287, Issue 5455, pp. 1049-1053
DOI: 10.1126/science.287.5455.1049

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Abstract

Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of the four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)–coupled PI3Kγ were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kγ−/− neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kγ-null macrophages showed a reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model. These results demonstrate that PI3Kγ is a crucial signaling molecule required for macrophage accumulation in inflammation.

  • * To whom correspondence should be addressed. E-mail: hirsch{at}molinette.unito.it and matthiaspaul.wymann{at}unifr.ch

  • These authors contributed equally to this work.

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