The intracellular signaling pathways involved in MCP-1-stimulated T cell migration across microvascular endothelium
The intracellular signaling pathways involved in MCP-1-stimulated T cell migration across microvascular endothelium
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DOI：
10.1006/cimm.1996.0035
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发表时间：
1996-02-01
影响因子：
4.3
通讯作者：
Chin, YH
中科院分区：
文献类型：
--
作者：
Cai, JP;Hudson, S;Chin, YH
T细胞通过微血管内皮的粘附和迁移是募集到炎性病变中的重要步骤，尽管刺激T细胞定向迁移的因素尚未完全表征。在本研究中，我们研究了趋化因子诱导T细胞迁移通过真皮微血管内皮细胞单层的能力。结果显示，重组MCP-1显著诱导静息和活化T细胞的跨内皮迁移。在10 ng/ml浓度和3- 4 h孵育期下观察到最大迁移诱导。相反，趋化因子IL-8、RANTES和MIP-1 α在高达100 ng/ml的剂量下未能刺激T细胞迁移。在旨在研究介导MCP-1效应的细胞内信号传导途径的研究中，结果显示，MCP-1在10至100 ng/ml的剂量范围内不会引起T细胞中细胞内钙离子的增加，即使这种趋化因子诱导单核细胞中的快速钙动员。此外，用双吲哚马来酰亚胺盐酸盐，一种蛋白激酶C的特异性抑制剂，或染料木素，一种蛋白酪氨酸激酶抑制剂，预处理T细胞，以剂量依赖性方式显着降低MCP-1诱导的迁移。相反，用蛋白激酶A特异性抑制剂H89预处理的T细胞对MCP-1刺激反应正常。最后，抗CD 11 a抗体可抑制T细胞的迁移，从而证实了β 2-整联蛋白在迁移过程中的重要性。(C)出版社：Academic Press，Inc.
The adherence and transmigration of T cells through microvascular endothelium is an essential step for recruitment into inflammatory lesions, although the factors that stimulate the directional migration of T cells have not been fully characterized. In the present study we investigated the capacity of chemokines to induce migration of T cells across dermal microvascular endothelial cell monolayer. The results showed that recombinant MCP-1 significantly induced transendothelial migration of both resting and activated T cells. Maximal induction of migration was observed at a concentration of 10 ng/ml and a 3- to 4-hr incubation period. In contrast, the chemokines IL-8, RANTES, and MIP-1 alpha failed to stimulate T cell migration at doses as high as 100 ng/ml. In studies designed to investigate the intracellular signaling pathways mediating the MCP-1 effect, the results showed that MCP-1 at doses ranging from 10 to 100 ng/ml did not cause an increase in intracellular calcium ions in T cells, even though this chemokine induced rapid calcium mobilization in monocytes. Furthermore, pretreatment of T cells with either bisindolymaleimide HCl, a specific inhibitor of protein kinase C, or genistein, a protein tyrosine kinase inhibitor, significantly decreased the MCP-1-induced transmigration in a dose-dependent manner. In contrast, T cells pretreated with the protein kinase A-specific inhibitor H89 responded normally to MCP-1 stimulation. Finally, T cell transmigration was inhibited by antibodies against CD11a, thereby confirming the importance of beta(2)-integrin in the transmigration process. (C) 1996 Academic Press, Inc.