Fc‐RECEPTOR CROSSLINKING STIMULATES CELL CYCLE PROGRESSION OF MACROPHAGES VIA THE ERK PATHWAY

Abstract

The signaling cascades responsible for, and resulting from, phagocytosis and cell division have been largely elucidated. Previously we demonstrated that macrophage cell proliferation was enhanced by phagocytosis and Fc receptors (FcR) crosslinking. In the present study, we further explored the activation of the signaling pathways by which Fc-mediated phagocytosis and IgG crosslinking may trigger cell cycle induction. FcR activation by Fc-mediated phagocytosis of live Cryptococcus neoformans, polystyrene beads, or IgG antibody crosslinking caused an increase in cyclin D1 protein expression in murine macrophages. In addition, we identified the extracellular signal-regulated kinase (ERK) signaling pathway as a potential mediator of signals from FcR activation to cyclin D1 expression, since cyclin D1 expression associated with FcR crosslinking was attenuated by PD98059, a specific inhibitor of the ERK1/2 signaling pathway. Given the ERK signaling pathway is activated by stimulation of many mitogens, our results imply that activation of FcR on macrophages may exert a mitogenic effect that subsequently stimulate macrophage proliferation. Our studies could lead to the identification of the precise signaling pathways involved in phagocytosis- or FcR activation-induced cell division and suggest a new target for therapy of certain diseases.