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Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation
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Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation
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Journal Article
Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation
2000
Overview
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.
Publisher
American Society for the Advancement of Science,American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Biological and medical sciences
/ Chemotactic Factors - pharmacology
/ Chemotaxis, Leukocyte - physiology
/ Coding
/ Fundamental and applied biological sciences. Psychology
/ Heterotrimeric GTP-Binding Proteins - metabolism
/ Kinases
/ Lordosis
/ Macrophages, Peritoneal - physiology
/ Mice
/ Molecular and cellular biology
/ Motility
/ Phosphatidylinositol 3-Kinases - metabolism
/ Phosphatidylinositol Phosphates - metabolism
/ Protein Serine-Threonine Kinases
/ Proteins
/ Proto-Oncogene Proteins - metabolism
