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(Journal of Leukocyte Biology. 2001;70:322-328.)
© 2001 by Society for Leukocyte Biology

FcR-mediated phagocytosis by human macrophages involves Hck, Syk, and Pyk2 and is augmented by GM-CSF

Katherine Kedzierska^*,, Nicholas J. Vardaxis, Anthony Jaworowski and Suzanne M. Crowe^*,*,

^* AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, and National Centre for HIV Virology Research, Fairfield;
Department of Medicine, Monash University, Prahran; and
Department of Medical Laboratory Science, Royal Melbourne Institute of Technology, Bundoora, Australia

Correspondence: Suzanne Crowe, AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Yarra Bend Rd., Fairfield, 3078 Melbourne, Australia. E-mail: crowe{at}burnet.edu.au

The receptors for the constant region of immunoglobulin G (FcR) are widely expressed on cells of hemopoietic lineage and plays an important role in host defense. We investigated the signaling pathways during FcR-mediated phagocytosis in human monocyte-derived macrophages (MDMs) and examined the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on these events. FcR-mediated phagocytosis resulted in enhanced tyrosine phosphorylation of a wide range of cellular proteins and activation of tyrosine kinases Hck, Syk, and Pyk2, as well as the multidomain adapter protein paxillin. Stimulation of MDMs with GM-CSF augmented FcR-mediated phagocytosis and increased the levels of tyrosine phosphorylation in phagocytosing MDM cultures, indicating tyrosine kinase-mediated activation. GM-CSF treatment of MDMs without a phagocytic stimulus did not activate Syk, suggesting that GM-CSF may act either distally to Syk in the FcR-mediated signaling cascade or on a parallel pathway activated by the FcR. This study shows that early signaling events during FcR-mediated phagocytosis in human MDMs involve activation of Syk, Hck, and paxillin. It also provides the first evidence for Pyk2 activation during phagocytosis and a baseline for further studies on the effect of GM-CSF on FcR-mediated phagocytosis.

Key Words: paxillin • monocyte-derived macrophage • tyrosine kinase • signaling

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