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

The receptors for the constant region of immunoglobulin G (Fc gammaR) are w idely expressed on cells of hemopoietic lineage and plays an important role in host defense. We investigated the signaling pathways during Fc gammaR-m ediated phagocytosis in human monocyte-derived macrophages (MDMs) and exami ned the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on these events. Fc gammaR-mediated phagocytosis resulted in enhanced tyro sine phosphorylation of a wide range of cellular proteins and activation of tyrosine kinases Hck, Syk, and Pyk2, as well as the multidomain adapter pr otein paxillin. Stimulation of MI)Ms with GM-CSF augmented Fc gammaR-mediat ed phagocytosis, and increased the levels of tyrosine phosphorylation in ph agocytosing MDM cultures, indicating tyrosine kinase-mediated activation. G M-CSF treatment of MI)Ms without a phagocytic stimulus did not activate Syk , suggesting that GMCSF may act either distally to Syk in the Fc gammaR-med iated signaling cascade or on a parallel pathway activated by the Fc gammaR . This study shows that early signaling events during Fc gammaR-mediated ph agocytosis in human MI)Ms involve activation of Syk, Hck, and paxillin. It also provides the first evidence for Pyk2 activation during phagocytosis an d a baseline for further studies on the effect of GM-CSF on Fc gammaR-media ted phagocytosis.