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 PI3Kgamma were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kgamma-/- neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kgamma-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 PI3Kgamma is a crucial signaling molecule required for macrophage accumulation in inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chemotactic Factors / pharmacology
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Chemotaxis*
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Chemotaxis, Leukocyte / physiology
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Enzyme Activation
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Gene Targeting
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Isoenzymes / metabolism
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Macrophages, Peritoneal / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neutrophils / metabolism
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Neutrophils / physiology*
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Peritonitis / enzymology
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Peritonitis / immunology*
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Peritonitis / pathology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphatidylinositol Phosphates / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Respiratory Burst
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Signal Transduction*
Substances
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Chemotactic Factors
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Isoenzymes
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Phosphatidylinositol Phosphates
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Proto-Oncogene Proteins
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phosphatidylinositol 3,4,5-triphosphate
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Heterotrimeric GTP-Binding Proteins