Analysis of CD26 mediated signal transduction mechanism.

CD26介导的信号转导机制分析。

• 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

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

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)活性，在T细胞共刺激中发挥重要作用。以β-趋化因子为趋化因子，检测CD26/二肽基肽酶IV在跨内皮细胞迁移中的作用。当可溶性重组CD26(sCD26/DPPIV^+)加入到经内皮细胞趋化系统中时，T细胞向RANTES的趋化迁移显著增强。在50 ng/mlRANTES中加入sCD26，与单独加入RANTES相比，迁移反应增强2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促进T细胞迁移的机制的过程中，我们发现在生理条件下，RANTES被sCD26在其酶特异性的精确位置上切割。然而，合成的RANTES缺乏两个N-末端的氨基a-…更多的CID对T细胞显示出相当于全长RANTES的趋化活性。与T细胞相比，截短的RANTES对纯化的单核细胞的趋化作用不明显，补充sCD26而不是mCD26可降低单核细胞对RANTES的趋化反应。这些结果提示CD26/DPPIV对RANTES的趋化反应具有差异性调节T细胞和单核细胞对RANTES的趋化反应，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1α(SDF-1α)是一种趋化因子，可预防T嗜性HIV毒株的感染，可能是CD26/DPPIV的底物。我们发现SDF-1α在N末端被CD26/DPPIV切割，导致SDF-1α对HIV感染的抑制作用消失。此外，SDF-1α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-1α促进T嗜性HIV毒株在体内的传播。较少

项目成果

Ohtsuki T: "Negative regulation of the anti‐HIV and chemotactic activity of human stromal cell-derived factor 1α by CD26/DPPIV." FEBS Letter. 431. 236-240 (1998)

Ohtsuki T：“CD26/DPPIV 对人基质细胞衍生因子 1α 的抗 HIV 和趋化活性的负调节。”FEBS Letter。431. 236-240 (1998)

Hegen M: "Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase." Immunol.90. 257-264 (1997)

Hegen M：“抗体交联 CD26 会诱导酪氨酸磷酸化和丝裂原激活蛋白激酶的激活。”

Hegen M,Kameoka J,Dong RP,Schlossman SF,and Morimoto C.: "Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase." Immunol.90. 257-264 (1997)

Hegen M、Kameoka J、Dong RP、Schlossman SF 和 Morimoto C.：“抗体交联 CD26 会诱导酪氨酸磷酸化和丝裂原激活蛋白激酶的激活。”

Dong R-P,Tachibana K,Hegen M,Soherpe S,Cho D,Schlossman SF,and Morimoto C.: "Correlation of the epitope defined by anti-CD26 mAbs and CD26 function." Mol.Immunol.35. 13-21 (1998)

Dong R-P、Tachibana K、Hegen M、Soherpe S、Cho D、Schlossman SF 和 Morimoto C.：“抗 CD26 mAb 定义的表位与 CD26 功能的相关性。”

Dong R-P,Umezawa Y,Ikushima H,Munakata Y,Schlossman SF,and Morimoto C.: "Different regulatory effects of pentoxifylline on human T cell activation pathways." J.Clin.Immunol.17. 247-252 (1997)

Dong R-P、Umezawa Y、Ikushima H、Munakata Y、Schlossman SF 和 Morimoto C.：“己酮可可碱对人类 T 细胞激活途径的不同调节作用。”