Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation.
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.
Hirsch
E
E
Department of Genetics, Biology and Biochemistry, University of Torino, Turin, Italy.
Katanaev
V L
VL
Garlanda
C
C
Azzolino
O
O
Pirola
L
L
Silengo
L
L
Sozzani
S
S
Mantovani
A
A
Altruda
F
F
Wymann
M P
MP
D000818:Animals; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004789:Enzyme Activation; D018390:Gene Targeting; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010538:Peritonitis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D016897:Respiratory Burst; D015398:Signal Transduction
D002630:Chemotactic Factors; D020962:Heterotrimeric GTP-Binding Proteins; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C060974:phosphatidylinositol 3,4,5-triphosphate