| Project/Area Number |
09044266
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MORIMOTO Chikao The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (30119028)
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| Co-Investigator(Kenkyū-buntansha) |
MUNAKATA Yasuhiko Harvard University, Dana-Farber Cancer Institute, Research Associate, ダナファーバー癌研究所, 研究員
IWATA Satoshi Harvard University, Dana-Farber Cancer Institute, Research Associate, ダナファーバー癌研究所, 研究員
HOSONO Osamu The University of Tokyo, Institute of Medical Science, Assistant Professor, 医科学研究所, 助手 (50190210)
シュロスマン スチュアー ハーバード大学, ダナファーバー癌研究所, 教授
SCHLOSSMAN Sf Harvard University, Dana-Farber Cancer Institute, Professor
ムナカタ ヤスヒコ ハーバード大学, ダナファーバー癌研究所, 研究員
トワタ サトシ ハーバード大学, ダナファーバー癌研究所, 研究員
シュロスマン スチューア ハーバード大学, ダナファーバー癌研究所, 教授
本間 利夫 東京大学, 医科学研究所, 教務職員 (10282526)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | 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 |
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| Research Abstract |
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
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