Differential regulation by leukotrienes and calcium of Fcγ receptor-induced phagocytosis and Syk activation in dendritic cells versus macrophages

Macrophage (MO) phagocytosis via the Fc receptor for immunoglobulin G (Fc gamma R) requires the spleen tyrosine kinase (Syk) and serves an important antimicrobial function. We have reported previously that Fc gamma R-mediated ingestion and Syk activation in MO are amplified by and depend on the proinflammatory lipid mediator leukotriene B-4, (LTB4). Although Fc gamma R-mediated ingestion is also important for antigen uptake, there is no information about LTB4 regulation of these processes in dendritic cells (DCs). In this study, we compared murine bone marrow (BM)-derived DCs to MO from BM, peritoneum, and the pulmonary alveolar space. Neither phagocytosis nor Syk activation in DCs was influenced by exogenous LTB4. Unlike the various MO populations, Syk activation in DCs was likewise unaffected by pharmacologic or genetic strategies to inhibit endogenous LTB4 synthesis or to block the high-affinity LTB4 receptor BLT1. DCs were refractory to regulation by LTB4 despite the fact that they expressed BLT1 and mobilized intracellular calcium in response to its ligation. This resistance to LTB4 in DCs instead reflected the fact that in contrast to MO, Syk activation in DCs was itself entirely independent of calcium. These results identify a fundamental difference in Fc gamma R signaling between DCs and MO, which may relate to the divergent, functional consequences of target ingestion in the two cell types.