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

Yong Luo, Jeffrey W. Pollard, Arturo Casadevall

Research output: Contribution to journalArticle

Abstract

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
Volume285
Issue number6
DOIs
StatePublished - Feb 5 2010
Externally publishedYes

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Fc Receptors
Macrophages
Extracellular Signal-Regulated MAP Kinases
Cell proliferation
Cell Proliferation
Chemical activation
Cell Cycle
Cyclin D1
Cells
MAP Kinase Signaling System
Pathogens
Phagocytosis
Mitosis
Protein-Tyrosine Kinases
Machinery
Communicable Diseases
Leukemia
Chronic Disease

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Fcγ receptor cross-linking stimulates cell proliferation of macrophages via the ERK pathway. / Luo, Yong; Pollard, Jeffrey W.; Casadevall, Arturo.

In: Journal of Biological Chemistry, Vol. 285, No. 6, 05.02.2010, p. 4232-4242.

Research output: Contribution to journalArticle

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