Class I phosphoinositide 3-kinase p110β is required for apoptotic cell and Fcγ receptor-mediated phagocytosis by macrophages

Abstract

Phosphoinositide 3-kinases (PI3Ks) play an important role in a variety of cellular functions, including phagocytosis. PI3Ks are activated during phagocytosis induced by several receptors and have been shown to be required for phagocytosis through the use of inhibitors such as wortmannin and LY294002. Mammalian cells have multiple isoforms of PI3K, and the role of the individual isoforms during phagocytosis has not been addressed. The class I PI3Ks consist of a catalytic p110 isoform associated with a regulatory subunit. Mammals have three genes for the class IA p110 subunits encoding p110α, p110β, and p110δ and one gene for the class IB p110 subunit encoding p110γ. Here we report a specific recruitment of p110β and p110δ (but not p110α) isoforms to the nascent phagosome during apoptotic cell phagocytosis by fibroblasts. By microinjecting inhibitory antibodies specific to class IA p110 subunits, we have shown that p110β is the major isoform required for apoptotic cell and Fcγ receptor-mediated phagocytosis by primary mouse macrophages. Macrophages from mice expressing a catalytically inactive form of p110δ showed no defect in the phagocytosis of apoptotic cells and IgG-opsonized particles, confirming the lack of a major role for p110δ in this process. Similarly, p110γ-deficient macrophages phagocytosed apoptotic cells normally. Our findings demonstrate that p110β is the major class I catalytic isoform required for apoptotic cell and Fcγ receptor-mediated phagocytosis by primary macrophages.