Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation

Emilio Hirsch; Vladimir L. Katanaev; Cecilia Garlanda; Ornella Azzolino; Luciano Pirola; Lorenzo Silengo; Silvano Sozzani; Alberto Mantovani; Fiorella Altruda; Matthias P. Wymann

doi:10.1126/science.287.5455.1049

Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation

Emilio Hirsch^*, Vladimir L. Katanaev, Cecilia Garlanda, Ornella Azzolino, Luciano Pirola, Lorenzo Silengo, Silvano Sozzani, Alberto Mantovani, Fiorella Altruda, Matthias P. Wymann

^*Corresponding author for this work

QBRI - Translational Oncology Research Center

Research output: Contribution to journal › Article › peer-review

1142 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	1049-1052
Number of pages	4
Journal	Science
Volume	287
Issue number	5455
DOIs	https://doi.org/10.1126/science.287.5455.1049
Publication status	Published - 11 Feb 2000

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title = "Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation",

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 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.",

author = "Emilio Hirsch and Katanaev, {Vladimir L.} and Cecilia Garlanda and Ornella Azzolino and Luciano Pirola and Lorenzo Silengo and Silvano Sozzani and Alberto Mantovani and Fiorella Altruda and Wymann, {Matthias P.}",

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AU - Hirsch, Emilio

AU - Katanaev, Vladimir L.

AU - Garlanda, Cecilia

AU - Azzolino, Ornella

AU - Pirola, Luciano

AU - Silengo, Lorenzo

AU - Sozzani, Silvano

AU - Mantovani, Alberto

AU - Altruda, Fiorella

AU - Wymann, Matthias P.

PY - 2000/2/11

Y1 - 2000/2/11

N2 - 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.

AB - 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.

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Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation

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