Syk and Lyn phosphorylation induced by FcγRI and FγRII crosslinking is determined by the differentiation state of U-937 monocytic cells

Fcγ receptor (FcγR)-mediated phagocytosis by mononuclear phagocytes is an essential function in host defense. This process is initiated by crosslinking of membrane FcγRs, which induces phosphorylation and activation of Src and Syk tyrosine kinases. Activation of these enzymes is essential for initiating the biochemical cascade that results in the cytoskeletal and membrane changes involved in phagocytosis. Phagocytic capacity and other effector functions of mononuclear phagocytes change during differentiation/maturation of these cells. This is a complex process governed by different soluble and micro-environmental factors, giving rise to populations of cells with distinct phenotypic characteristics. Several agents, including calcitriol, have been shown to induce in vitro differentiation-related phenotypic changes in monocytic cell lines. In this paper, we characterized the changes in the initial biochemical signals associated with the increase in FcγR-mediated phagocytosis induced by calcitriol in monocytic U-937 cells. The 10-fold increase in phagocytic capacity is not accompanied by an increase in FcγR expression. However, the phosphorylation levels of Lyn and Syk after FcγRI or FcγRII crosslinking are increased after calcitriol treatment. Our results suggest that signaling induced by FcγR in mononuclear phagocytes is not only dependent on the quantity of FcγRs aggregated by a stimulus, but it is highly dependent on the cell's differentiation state.