Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation.
Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation.
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发表时间：
2000
期刊：
影响因子：
56.9
通讯作者：
E. Hirsch;V. Katanaev;C. Garlanda;O. Azzolino;L. Pirola;L. Silengo;S. Sozzani;A. Mantovani;F. Altruda;M. Wymann
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文献类型：
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作者：
E. Hirsch;V. Katanaev;C. Garlanda;O. Azzolino;L. Pirola;L. Silengo;S. Sozzani;A. Mantovani;F. Altruda;M. Wymann
磷酸肌醇 3 激酶 (PI3K) 活性对于白细胞功能至关重要，但四种受体激活亚型的作用尚不清楚。缺乏异三聚体鸟嘌呤核苷酸结合蛋白（G 蛋白）偶联 PI3Kgamma 的小鼠能够存活，并且具有完全分化的中性粒细胞和巨噬细胞。趋化剂刺激的 PI3Kgamma-/- 中性粒细胞不产生磷脂酰肌醇 3,4,5-三磷酸，不激活蛋白激酶 B，并且表现出呼吸爆发和运动受损。在脓毒症腹膜炎模型中，腹膜 PI3Kgamma 缺失的巨噬细胞向各种趋化刺激的迁移减少，并且积累严重缺陷。这些结果表明 PI3Kgamma 是炎症中巨噬细胞积聚所需的关键信号分子。
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.