Protease-activated receptor-2 signaling triggers dendritic cell development
Protease-activated receptor-2 signaling triggers dendritic cell development
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DOI：
10.1016/s0002-9440(10)64316-7
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发表时间：
2003-06-01
影响因子：
6
通讯作者：
Lawson, JH
中科院分区：
文献类型：
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作者：
Fields, RC;Schoenecker, JG;Lawson, JH
树突状细胞（DC）是一种有效的抗原提呈细胞，控制效应细胞。免疫系统的反应。DC被认为是在由炎症刺激加速的过程中从循环祖细胞持续发育。然而，调节DC从前体细胞发育的生理信号尚未得到很好的定义。在这里，我们表明，丝氨酸蛋白酶通过蛋白酶激活受体-2（PAR-2）的作用，刺激骨髓祖细胞培养的粒细胞-巨噬细胞集落刺激因子和IL-4的DC的发展。用大豆胰蛋白酶抑制剂（一种丝氨酸蛋白酶抑制剂）处理的骨髓培养物中，DC不能发育，但这种抑制作用可被PAR-2激动剂肽克服。树突状细胞不能从PAR-2缺陷小鼠的骨髓中自发发育，但可以通过炎症介质刺激而这样做。这些结果表明，内源性丝氨酸蛋白酶刺激体外DC发育。因此，丝氨酸蛋白酶可以帮助触发体内适应性免疫应答。
Dendritic cells (DC) are potent antigen-presenting cells that govern the effector cell. responses of the immune system. DC are thought to continuously develop from circulating progenitors in a process that is accelerated by inflammatory stimuli. However, the physiological signals that regulate the development of DC from precursor cells have not been well defined. Here we show that a serine protease acting via protease-activated receptor-2 (PAR-2) stimulates the development of DC from bone marrow progenitor cells cultured in granulocyte-macrophage colony-stimulating factor and IL-4. DC fail to develop in bone marrow cultures treated with soy bean trypsin inhibitor, a serine protease inhibitor, but this inhibition is overcome by a PAR-2 agonist peptide. DC do not spontaneously develop from the bone marrow of PAR-2-deficient mice, but can be stimulated to do so by inflammatory mediators. These results suggest that endogenous serine proteases stimulate DC development in vitro. Thus, serine proteases may help trigger adaptive immune responses in vivo.