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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2003-02-0534. This Article Full Text (PDF) All Versions of this Article: 2003-02-0534v1 102/5/1877    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by de Azevedo Canetti, C. Articles by Peters-Golden, M. Search for Related Content PubMed PubMed Citation Articles by de Azevedo Canetti, C. Articles by Peters-Golden, M. Social Bookmarking                   What's this? Submitted February 20, 2003 Accepted April 21, 2003 Syk activation is a leukotriene B4-regulated event involved in macrophage phagocytosis of IgG-coated targets but not apoptotic cells Claudio de Azevedo Canetti, Bin Hu, Jeffrey L Curtis, and Marc Peters-Golden* Department of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA Department of Pulmonary and Critical Care Medicine, VA Medical Center, Ann Arbor, MI, USA * Corresponding author; email: petersm{at}umich.edu. Macrophages are called upon to ingest both IgG-coated targets and apoptotic cells. Important roles for tyrosine kinase Syk and leukotriene B4 (LTB4) are recognized in FcR-mediated phagocytosis. Here we evaluated the roles of Syk and of LTB4 in macrophage phagocytosis of apoptotic thymocytes vs. IgG-coated erythrocytes. Macrophages ingestion of apoptotic thymocytes was not influenced by exogenous or endogenous LTB4, nor associated with Syk activation (phosphorylation). By contrast, LTB4 dose-dependently amplified FcR-mediated phagocytosis as well as Syk activation. Furthermore, a role for endogenous LTB4 in Syk activation during FcR-mediated phagocytosis was demonstrated using pharmacologic and genetic abrogation of 5-lipoxygenase. LTB4 was unique among 5-lipoxygenase products in this regard, since LTD4 and 5-HETE were unable to amplify Syk activation in response to FcR engagement. Ca2+ chelation studies revealed that FcR-mediated Syk activation as well as LTB4 amplification thereof were Ca2+-regulated. These two parallel phagocytic processes therefore exhibit initial divergence in signal transduction events, with Syk activation being a LTB4-regulated event in FcR-mediated but not apoptotic cell ingestion. As LTB4 is an important pro-inflammatory product of macrophages, we speculate that this divergence evolved to permit FcR-mediated phagocytosis to proceed in an inflammatory milieu while apoptotic cell clearence is non-inflammatory. 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