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Analysis of CD26 mediated signal transduction mechanism.

CD26介导的信号转导机制分析。

基本信息

批准号：
09044266
负责人：
MORIMOTO Chikao
金额：
$ 2.56万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044266/
关键词：
CD26 Dipeptidyl peptidase IV Chemokine RANTES SDF-1alpha Lymphocyte migration HIV infection Dipeptidyl peptidase IV SDF-1α Adenosine diaminase CDメモリーT細胞アデノシン

项目摘要

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

CD 26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。使用β-趋化因子作为化学引诱物检测了CD 26/二肽基肽酶IV在跨内皮迁移中的功能。当可溶性重组CD 26（sCD 26/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。添加sCD 26到50 ng/ml的RANTES增强迁移反应的一个因素的两个单独的RANTES相比，而突变的可溶性CD 26，缺乏DPPIV酶的活性，没有增强作用RANTES诱导的T细胞迁移。在分析sCD 26增强T细胞迁移的机制的过程中，我们发现RANTES在生理条件下在其酶特异性的精确位点被sCD 26切割。然而，合成的RANTES缺乏两个N-末端氨基， ...更多信息 cids对T细胞显示出与全长RANTES相当的趋化活性。此外，添加sCD 26可增强两种形式RANTES诱导的T细胞迁移。与T细胞相反，截短的RANTES对纯化单核细胞的趋化性无活性，并且添加sCD 26（而不是mCD 26）可降低单核细胞对RANTES的迁移反应。这些结果表明CD 26/DPPIV差异调节T细胞和单核细胞对RANTES的趋化反应，此外，这一发现可以部分解释体内慢性炎症部位的优势表型。基质细胞衍生因子1 α（SDF-1 α）是一种趋化因子，已被证明可以防止T嗜性HIV株的感染，并且是CD 26/DPPIV的可能底物。我们已经证明，SDF-1 α在N-末端区域被CD 26/DPPIV切割，因此，SDF-1 α对HIV感染的抑制活性消失。此外，SDF-1 α的趋化活性也被重组可溶性CD 26的DPPIV活性特异性地消除。这些结果表明，T嗜性HIV株在体内的传播可能是通过CD 26/DPPIV通过功能性SDF-1 α的失活而促进的。少