Preferential chemotaxis of activated human CD4+ T cells by extracellular cyclophilin A
Preferential chemotaxis of activated human CD4+ T cells by extracellular cyclophilin A
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DOI：
10.1189/jlb.0506317
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发表时间：
2007-09-01
影响因子：
5.5
通讯作者：
Constant, Stephanie L.
中科院分区：
文献类型：
--
作者：
Damsker, Jesse M.;Bukrinsky, Michael I.;Constant, Stephanie L.
白细胞的招募和运输是炎症过程的重要方面。尽管趋化因子被认为是细胞运输的主要调节因子，但最近已证明细胞外亲环蛋白对人类白细胞具有有效的趋化特性。亲环蛋白由多种细胞类型分泌，并且在持续炎症的组织中检测到高水平。 CD147 已被确定为人类白细胞上亲环蛋白 A (CypA) 的主要信号受体。有趣的是，来自发炎组织的白细胞上的 CD147 表达升高，表明细胞外亲环蛋白的存在、CD147 表达和炎症反应之间存在相关性。因此，亲环蛋白-CD147相互作用可能直接导致白细胞募集到发炎组织中。在目前的研究中，我们表明，与静息 T 细胞相比，活化的人 T 淋巴细胞表达的 CD147 水平升高，并且这些活化的 T 细胞比静息细胞更容易迁移到 CypA。此外，我们发现，与静息CD4+T细胞不同，亲环蛋白介导的活化T细胞迁移不需要与硫酸乙酰肝素受体相互作用，而是仅依赖于CD147相互作用。这些发现表明，当白细胞处于激活状态时，例如在炎症反应期间，亲环蛋白-CD147 相互作用将最有效。因此，靶向亲环蛋白-CD147相互作用可能提供一种减轻组织炎症的新方法。
The recruitment and trafficking of leukocytes are essential aspects of the inflammatory process. Although chemokines are thought to be the main regulators of cell trafficking, extracellular cyclophilins have been shown recently to have potent chemoattracting properties for human leukocytes. Cyclophilins are secreted by a variety of cell types and are detected at high levels in tissues with ongoing inflammation. CD147 has been identified as the main signaling receptor for cyclophilin A (CypA) on human leukocytes. It is interesting that the expression of CD147 is elevated on leukocytes from inflamed tissue, suggesting a correlation among the presence of extracellular cyclophilins, CD147 expression, and inflammatory responses. Thus, cyclophilin-CD147 interactions may contribute directly to the recruitment of leukocytes into inflamed tissues. In the current studies, we show that activated human T lymphocytes express elevated levels of CD147, compared with resting T cells and that these activated T cells migrate more readily to CypA than resting cells. Furthermore, we show that unlike resting CD4(+) T cells, the cyclophilin-mediated migration of activated T cells does not require interaction with heparan sulfate receptors but instead, is dependent on CD147 interaction alone. Such findings suggest that cyclophilin-CD147 interactions will be most potent when leukocytes are in an activated state, for example, during inflammatory responses. Thus, targeting cyclophilin-CD147 interactions may provide a novel approach for alleviating tissue inflammation.