Syk activation is a leukotriene B4-regulated event involved in macrophage phagocytosis of IgG-coated targets but not apoptotic cells
Syk activation is a leukotriene B4-regulated event involved in macrophage phagocytosis of IgG-coated targets but not apoptotic cells
复制标题
DOI：
10.1182/blood-2003-02-0534
复制
发表时间：
2003-09-01
期刊：
影响因子：
20.3
通讯作者：
Peters-Golden, M
中科院分区：
文献类型：
--
作者：
Canetti, C;Hu, B;Peters-Golden, M
巨噬细胞被要求摄取IgG包被的靶标和凋亡细胞。酪氨酸激酶Syk和白三烯B-4（LTB 4）在Fc γ R介导的吞噬作用中的重要作用已得到确认。在这里，我们评估了Syk和LTB 4在巨噬细胞吞噬凋亡的胸腺细胞与IgG包被的红细胞中的作用。巨噬细胞摄取凋亡的胸腺细胞不受外源性或内源性LTB 4的影响，也不与Syk激活（磷酸化）。相比之下，LTB 4剂量依赖性地扩增Fc γ R介导的吞噬作用以及Syk活化。此外，使用5-脂氧合酶的药理学和遗传学废除证明了内源性LTB 4在Fc γ R介导的吞噬作用期间在Syk活化中的作用。在这方面，LTB 4在5-脂氧合酶产物中是独特的，因为LTD 4和5-羟基二十碳四烯酸（HETE）不能响应于Fc γ R接合而扩增Syk活化。Ca 2+螯合研究表明，FegammaR介导的Syk激活以及LTB 4扩增是Ca 2+调节的。因此，这2个平行的吞噬过程在信号转导事件中表现出初始分歧，Syk激活是FcgammaR介导的LTB 4调节事件，而不是凋亡细胞摄取。由于LTB 4是巨噬细胞的重要促炎产物，我们推测这种分歧演变为允许Fc γ R介导的吞噬作用在炎症环境中进行，而凋亡细胞清除是非炎症性的。
Macrophages are called upon to ingest both IgG-coated targets and apoptotic cells. Important roles for tyrosine kinase Syk and leukotriene B-4 (LTB4) are recognized in FcgammaR-mediated phagocytosis. Here we evaluated the roles of Syk and LTB4 in macrophage phagocytosis of apoptotic thymocytes versus IgG-coated erythrocytes. Macrophage ingestion of apoptotic thymocytes was not influenced by exogenous or endogenous LTB4 nor associated with Syk activation (phosphorylation). By contrast, LTB4 dose-dependently amplified FcgammaR-mediated phagocytosis as well as Syk activation. Furthermore, a role for endogenous LTB4 in Syk activation during FcgammaR-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-hydroxyeicosatetraenoic acid (HETE) were unable to amplify Syk activation in response to FcgammaR engagement. Ca2+ chelation studies revealed that FegammaR-mediated Syk activation as well as LTB4 amplification thereof was Ca2+ regulated. These 2 parallel phagocytic processes therefore exhibit initial divergence in signal transduction events, with Syk activation being an LTB4-regulated event in FcgammaR-mediated but not apoptotic cell ingestion. As LTB4 is an important proinflammatory product of macrophages, we speculate that this divergence evolved to permit FcgammaR-mediated phagocytosis to proceed in an inflammatory milieu, while apoptotic cell clearance is noninflammatory.