Fc gamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn

Macrophage Fc gamma receptors (Fc gamma Rs) mediate the uptake and destruct ion of antibody-coated viruses, bacteria, and parasites. We examined Fc gam ma R signaling and phagocytic function in bone marrow-derived macrophages f rom mutant mice lacking the major Src family kinases ex pressed in these ce lls, Hck, Fgr, and Lyn. Many Fc gamma R-induced functional responses and si gnaling events were diminished or delayed in these macrophages, including i mmunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, act in cup formation, and activation of Syk, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinases 1 and 2, Significant reduction of I gG-dependent phagocytosis was not seen in hck(-/-)fgr(-/-) or lyn(-/-) cell s, although the single mutant lyn(-/-) macrophages did manifest signaling d efects. Thus, Src family kinases clearly have roles in two events leading t o Fc gamma R-mediated phagocytosis, one involving initiation of actin polym erization and the second involving activation of Syk and subsequent interna lization. Since Fc gamma R-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src fan-Lily kina ses are not absolutely required for uptake of IgG-opsonized particles.