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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)1049-1052
Number of pages4
JournalScience
Volume287
Issue number5455
DOIs
Publication statusPublished - Feb 11 2000

ASJC Scopus subject areas

  • General

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