Published online before print March 30, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0705374

Received for publication July 9, 2005.
Revised August 18, 2005.
Accepted for publication February 22, 2006.

Article

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

Claudio Canetti ^*, David M. Aronoff ^*, Mun Choe ^*, Nicolas Flamand ^*, Scott Wettlaufer ^*, Galen B. Toews ^*, Gwo-Hsiao Chen ^*, and Marc Peters-Golden ^*@

Divisions of *Pulmonary and Critical Care Medicine and Infectious Diseases, University of Michigan Health System, Ann Arbor; and Departamento de Farmacologia, Universidade do Estado do Rio de Janeiro, Brazil

Abstract

Macrophage (M) phagocytosis via the Fc receptor for immunoglobulin G (FcR) requires the spleen tyrosine kinase (Syk) and serves an important antimicrobial function. We have reported previously that FcR-mediated ingestion and Syk activation in M are amplified by and depend on the proinflammatory lipid mediator leukotriene B₄ (LTB₄). Although FcR-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 M from BM, peritoneum, and the pulmonary alveolar space. Neither phagocytosis nor Syk activation in DCs was influenced by exogenous LTB₄. Unlike the various M 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 M, Syk activation in DCs was itself entirely independent of calcium. These results identify a fundamental difference in FcR signaling between DCs and M, which may relate to the divergent, functional consequences of target ingestion in the two cell types.

Key Words: innate immunity • lipid mediators • cell signaling

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