Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix
Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix
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DOI：
10.1073/pnas.052284899
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发表时间：
2002-03-05
影响因子：
11.1
通讯作者：
Spik, G
中科院分区：
文献类型：
--
作者：
Allain, F;Vanpouille, C;Spik, G
亲环素A和亲环素B（CyPA和CyPB）是参与炎症事件的环孢菌素A结合蛋白。我们已经报道了CyPB与两种类型的细胞表面结合位点相互作用。第一个位点对应于功能性受体，并且需要与CyPB的中央核心相互作用。该区域在亲环素中高度保守，表明CyPA和CyPB可能通过与该受体的相互作用而介导共同的生物活性。第二个位点被鉴定为糖胺聚糖（GAGS），其结合区位于CyPB的N末端。CyPA和CyPB的N-末端延伸的差异表明与GAGS的独特相互作用可能是CyPB的选择性活性的原因。为了探索这一假设，我们分析了由CyPA、CyPB和CyPBKKK-_（一种不能与GAGS相互作用的突变体）触发的淋巴细胞应答。这三种配体似乎有足够的能力通过与相同的信号受体结合来引发钙信号和趋化性。相反，只有CyPB增强了T细胞与细胞外基质的牢固粘附。这种活性依赖于与GAGS和信号受体的相互作用。CyPB介导的粘附需要CD 147，这可能是因为它是一种共刺激分子，与α 4 β 1和α 4 β 7整合素的活化有关。最后，我们发现CyPB主要能够增强CD 4（+）CD 45 RO（+）亚群的T细胞粘附。目前的数据表明，CyPB而不是CyPA是T淋巴细胞的促炎因子，并强调了CyPB-GAG相互作用在该蛋白的趋化因子样活性中的关键作用。
Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGS), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGS might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPBKKK-_, a mutant unable to interact with GAGS. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGS and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of alpha4beta1 and alpha4beta7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4(+)CD45RO(+) subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB-GAG interaction in the chemokine-like activity of this protein.