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

Yong Luo, Jeffrey W. Pollard, Arturo Casadevall

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Macrophage proliferation can be stimulated by phagocytosis and by cross-linking of Fcγ receptors (FcγR). In this study, we investigated the role of FcγR and the signaling cascades that link FcγR activation to cell cycle progression. This effect was mediated by the activating FcγR, including FcγRI and III, via their Fcγ subunit. Further investigation revealed that the cell cycle machinery was activated by FcγR cross-linking through downstream signaling events. Specifically, we identified the extracellular signal-regulated kinase (ERK) signaling pathway as a mediator of signals from FcγR activation to cyclin D1 expression, because cyclin D1 expression associated with FcγR 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 FcγR activation produces a mitogenic effect that stimulates macrophage proliferation. Macrophage mitosis following FcγR 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 FcγR-stimulated macrophage cell proliferation.

Original languageEnglish (US)
Pages (from-to)4232-4242
Number of pages11
JournalJournal of Biological Chemistry
Issue number6
StatePublished - Feb 5 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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