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Publication : Phosphoinositide 3-kinase γ mediates microglial phagocytosis via lipid kinase-independent control of cAMP.

First Author  Schmidt C Year  2013
Journal  Neuroscience Volume  233
Pages  44-53 PubMed ID  23276671
Mgi Jnum  J:196425 Mgi Id  MGI:5487904
Doi  10.1016/j.neuroscience.2012.12.036 Citation  Schmidt C, et al. (2013) Phosphoinositide 3-kinase gamma mediates microglial phagocytosis via lipid kinase-independent control of cAMP. Neuroscience 233:44-53
abstractText  Microglial phagocytosis plays a key role in neuroprotective and neurodegenerative responses of the innate immune system in the brain. Here we investigated the regulatory function of phosphoinositide 3-kinase gamma (PI3Kgamma) in phagocytosis of bacteria and Zymosan particles by mouse brain microglia in vitro and in vivo. Using genetic and pharmacological approaches our data revealed PI3Kgamma as an essential mediator of microglial phagocytosis. Unexpectedly, microglia expressing lipid kinase deficient mutant PI3Kgamma exhibited similar phagocytosis as wild-type cells. These data suggest kinase-independent stimulation of cAMP phosphodiesterase activity by PI3Kgamma as a crucial mediator of phagocytosis. In sum our findings indicate PI3Kgamma-dependent suppression of cAMP signaling as a critical regulatory element of microglial phagocytosis.
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