Extracellular cyclophilins contribute to the regulation of inflammatory responses
Extracellular cyclophilins contribute to the regulation of inflammatory responses
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DOI：
10.4049/jimmunol.175.1.517
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Constant, SL
中科院分区：
文献类型：
--
作者：
Arora, K;Gwinn, WM;Constant, SL
炎症反应期间白细胞运输的主要调节因子是趋化因子。然而，最近发现的另一类趋化剂是细胞外亲环素，这种蛋白质通常被称为免疫抑制药物环孢素A的受体。亲环素可以在体外诱导白细胞趋化性，并已在炎症组织中检测到升高的水平，表明它们可能有助于炎症反应。我们最近发现CD 147是亲环素A的主要信号受体。在目前的研究中，我们研究了亲环蛋白-CD 147相互作用的贡献，在体内炎症反应，使用小鼠模型的急性肺损伤。通过靶向CD 147（使用抗CD 147 Ab）或亲环蛋白（使用非免疫抑制性环孢素A类似物）阻断亲环蛋白-CD 147相互作用可使组织嗜中性粒细胞减少高达50%，同时减少组织病理学。这些发现首次证明了亲环素对炎症反应的重要贡献，并为减少炎症介导的疾病提供了一种潜在的新方法。
The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases.