Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production
Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production
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DOI：
10.1182/blood-2005-03-1239
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发表时间：
2005-10-01
期刊：
影响因子：
20.3
通讯作者：
Simmons, RM
中科院分区：
文献类型：
--
作者：
Underhill, DM;Rossnagle, E;Simmons, RM
Dectin-1是β-葡聚糖的凝集素受体，对真菌的先天巨噬细胞识别很重要，并有助于吞噬作用、活性氧产生和诱导炎性细胞因子。Dectin-1介导细胞内信号传导的机制刚刚开始被定义。脾酪氨酸激酶（Syk）是一种蛋白质酪氨酸激酶，对适应性免疫应答至关重要，它通过B细胞受体、T细胞受体和Fc受体介导信号传导。在这里，我们报告说，Dectin-1激活Syk在巨噬细胞和Dectin-1刺激的活性氧产生是重要的，但不是吞噬作用。Syk激活仅限于巨噬细胞亚群;与不能激活该途径的细胞处于平衡状态。使用这种信号传导途径的巨噬细胞的比例可以通过细胞因子处理来调节。因此，Dectin-1信号转导揭示了炎症激活潜力中的动态巨噬细胞异质性。
Dectin-1 is a lectin receptor for beta-glucan that is important for innate macrophage recognition of fungi and contributes to phagocytosis, reactive oxygen production, and induction of inflammatory cytokines. The, mechanisms by which Dectin-1 mediates intracellular signaling are just beginning to, be defined. Spleen tyrosine kinase (Syk) is a protein, tyrosine kinase that is critical for adaptive immune responses where it mediates signaling through B-cell receptors, T-cell receptors, and Fc receptors. Here we report that Dectin-1 activates Syk in macrophages and is important for Dectin-1-stimulated reactive oxygen production, but not for phagocytosis. Syk activation is restricted to a subpopulation of macrophages; that is in equilibrium with cells that cannot activate the pathway. The proportion of macrophages using this signaling pathway can be modulated by cytokine treatment. Thus, Dectin-1 signaling reveals dynamic macrophage heterogeneity in inflammatory activation potential.