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

Fc gamma receptor (Fc gamma R)-mediated phagocytosis by mononuclear phagocytes is an essential function in host defense. This process is initiated by crosslinking of membrane Fc gamma Rs, 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 Fc gamma R-mediated phagocytosis induced by calcitriol in monocytic U-937 cells. The 10-fold increase in phagocytic capacity is not accompanied by an increase in Fc gamma R expression. However, the phosphorylation levels of Lyn and Syk after Fc gamma RI or Fc gamma RII crosslinking are increased after calcitriol treatment. Our results suggest that signaling induced by Fc gamma R in mononuclear phagocytes is not only dependent on the quantity of Fc gamma Rs aggregated by a stimulus, but it is highly dependent on the cell's differentiation state. (c) 2005 Elsevier B.V. All rights reserved.