Publikationsdatum:
2000-02-11
Beschreibung:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hirsch, E -- Katanaev, V L -- Garlanda, C -- Azzolino, O -- Pirola, L -- Silengo, L -- Sozzani, S -- Mantovani, A -- Altruda, F -- Wymann, M P -- E.0635/Telethon/Italy -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1049-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Biology and Biochemistry, University of Torino, Turin, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669418" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
Chemotactic Factors/pharmacology
;
*Chemotaxis
;
Chemotaxis, Leukocyte/physiology
;
Enzyme Activation
;
Gene Targeting
;
Heterotrimeric GTP-Binding Proteins/*metabolism
;
Isoenzymes/metabolism
;
Macrophages, Peritoneal/*physiology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Neutrophils/metabolism/*physiology
;
Peritonitis/enzymology/*immunology/pathology
;
Phosphatidylinositol 3-Kinases/*metabolism
;
Phosphatidylinositol Phosphates/metabolism
;
*Protein-Serine-Threonine Kinases
;
Proto-Oncogene Proteins/metabolism
;
Proto-Oncogene Proteins c-akt
;
Respiratory Burst
;
*Signal Transduction
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
