Analysis of CD26 mediated signal transduction mechanism.

CD26是一种110 kDa的细胞表面糖蛋白，具有二肽基肽酶IV （DPPIV; EC3.4.14.5）酶活性，在T细胞共刺激中起重要作用。采用β趋化因子作为趋化剂，检测CD26/二肽基肽酶IV在跨内皮细胞迁移中的功能。当可溶性重组CD26 （sCD26/DPPIV^+）加入到跨内皮趋化系统中时，T细胞向RANTES的趋化迁移显著增强。将sCD26添加到50 ng/ml的RANTES中，与单独使用RANTES相比，其迁移反应增强了两倍，而缺乏DPPIV酶活性的突变型可溶性CD26对RANTES诱导的T细胞迁移没有增强作用。在分析sCD26增强T细胞迁移的机制过程中，我们发现RANTES在生理条件下被sCD26在其酶特异性特征的精确位点上切割。然而，合成的缺乏两个n端氨基酸的RANTES在T细胞上表现出与全长RANTES相当的趋化活性。此外，sCD26的加入还能增强两种RANTES诱导的T细胞迁移。与T细胞相比，截断的RANTES对纯化的单核细胞的趋化性不活跃，补充sCD26而不是mCD26降低了单核细胞对RANTES的迁移反应。这些结果表明，CD26/DPPIV对T细胞和单核细胞对RANTES的趋化反应有差异调节，此外，这一发现可以部分解释体内慢性炎症部位的显性表型。基质细胞衍生因子1 α (sdf -1 α)是一种趋化因子，已被证明可以预防嗜t型HIV毒株的感染，并且可能是CD26/DPPIV的底物。我们已经证明SDF-1alpha在n端被CD26/DPPIV切割，导致SDF-1alpha对HIV感染的抑制活性消失。此外，SDF-1alpha的趋化活性也被重组可溶性CD26的DPPIV活性特异性地消失。这些结果表明，CD26/DPPIV可能通过失活功能性sdf -1 α促进嗜t型HIV毒株在体内的传播。少

CD26, a 110 kDa cell surface glycoprotein, exhibits dipeptidyl peptidase IV (DPPIV ; EC3.4.14.5) enzyme activity and plays an important role in T cell costimulation. the function of CD26/dipeptidyl peptidase IV in transendothelial migration was examined using beta-chemokines as chemoattractants. When soluble recombinant CD26 (sCD26/DPPIV^+) was added to the transendothelial chemotaxis system, chemotactic migration of T cells toward RANTES was significantly enhanced. Addition of sCD26 to 50 ng/ml of RANTES enhanced the migratory response by a factor of two compared to RANTES alone, whereas mutant soluble CD26, lacking the DPPIV enzyme activity, had no enhancing effect on RANTES-induced T cell migration. In the process of analyzing the mechanisms of the enhancement of T cell migration by sCD26, we showed that RANTES was cleaved by sCD26 under physiologic conditions at the precise site characteristic of its enzyme specificity. However, synthesized RANTES which lacks two N-terminal amino a … More cids showed a chemotactic activity equivalent to full length RANTES on T cells. Furthermore, addition of sCD26 showed enhancement of T cell migration induced by both forms of RANTES.In contrast to T cells, the truncated RANTES is inactive in chemotaxis of purified monocytes, and supplement of sCD26 but not mCD26 reduced the migratory response of monocytes to RANTES.These results suggest that CD26/DPPIV differentially regulate the chemotactic response of T cells and monocytes to RANTES and furthermore, the finding can partly explain the dominant phenotype at the chronic inflammatory sites in vivo. Stromal cell-derived factor 1alpha (SDF-1alpha) is a chemokine that has been shown to prevent infection of T-tropic HIV strains and is a possible substrate of CD26/DPPIV.We have shown that SDF-1alpha was cleaved at the N-terminal region by CD26/DPPIV and as a result, the inhibitory activity of SDF-1alpha against HIV infection was disappeared. Moreover, the chemotactic activity of SDF-1alpha was also disappeared specifically by DPPIV activity of recombinant soluble CD26. These results suggested that dissemination of T-tropic HIV strains in vivo may be facilitated by CD26/DPPIV via inactivation of functional SDF-1alpha. Less