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J Biol Chem. 2010 Feb 5;285(6):4232-42. doi: 10.1074/jbc.M109.037168. Epub 2009 Dec 8.

Fcgamma receptor cross-linking stimulates cell proliferation of macrophages via the ERK pathway.

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  • 1Departments of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Abstract

Macrophage proliferation can be stimulated by phagocytosis and by cross-linking of Fcgamma receptors (FcgammaR). In this study, we investigated the role of FcgammaR and the signaling cascades that link FcgammaR activation to cell cycle progression. This effect was mediated by the activating FcgammaR, including FcgammaRI and III, via their Fcgamma subunit. Further investigation revealed that the cell cycle machinery was activated by FcgammaR cross-linking through downstream signaling events. Specifically, we identified the extracellular signal-regulated kinase (ERK) signaling pathway as a mediator of signals from FcgammaR activation to cyclin D1 expression, because cyclin D1 expression associated with FcgammaR cross-linking was attenuated by specific inhibitors of the ERK1/2 signaling pathway, PD98059 and U0126 and the spleen tyrosine kinase (Syk) inhibitor, Piceatannol. Our findings establish a link between the ERK activation and cell cycle signaling pathways, thus providing a causal mechanism by which FcgammaR activation produces a mitogenic effect that stimulates macrophage proliferation. Macrophage mitosis following FcgammaR activation could potentially affect the outcome of macrophage interactions with intracellular pathogens. In addition, our results suggest the possibility of new treatment options for certain infectious diseases, chronic inflammatory diseases, and leukemias based on interference with FcgammaR-stimulated macrophage cell proliferation.

PMID:
19996316
[PubMed - indexed for MEDLINE]
PMCID:
PMC2823562
Free PMC Article

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