2002 Fiscal Year Final Research Report Summary
Study on the Rationale of Prevention of chronic allograft rejection explored by Inhibitory compound of macrophage-effector generation
| Project/Area Number |
13671670
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Nara Medical University |
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Principal Investigator |
ISHIBASHI Michio Nara Medical University, Department of Urology, Assistant Professor, 医学部, 講師 (40107032)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Kyohide Nara Medical University, Department of Urology, Research Associate, 医学部, 助手 (50264867)
YOSHIDA Katsunori Nara Medical University, Department of Urology, Associate Professor, 医学部, 助教授 (50192422)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Macrophage / CD11b of β2-integrin / chronic allograft rejection / unilateral ureteral obstruction / chemokine receptor / ケモカインレセプター |
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| Research Abstract |
PURPOSE The main obstacle of long -term acceptance of transplanted allograft is chronic allograft (CA) rejection. Although T cells and macrophages (Mf) are suggested to be involved in, the mechanism of CA rejection mediated by those immune cells is obscure. We developed the new inhibitory compound, gammalactone, of Mf-effector generation. Gammalactone inhibits the generation of Mf-effector, designated as Spontaneous Plaque-Forming Cell(SPFC) , in which SPFC is mediated by CD11/CD18 β2-integrin. In the present study, we investigated which kinds of molecules expressed on Mf-effector are involved in CA rejection of human renal transplant and in renal fibrosis of experimental progressive renal disease in rats. RESULTS & Discussion In biopsy specimen of human renal allograft of CA rejection, CD11b positive cells , which are expressed on Mf, CD5+B cells or NK cells, were detected more significantly than CD5-positive cells. Using the modified model of unilateral ureteral obstruction for 14 days following release for 7days in SD rats, gammalactone was administered for 21 days throughout the study. The glomerular and tubulointerstitial lesions in animals treated with gammalactone were ameliorated more significantly than the untreated control animals. The CD11b-positive cells were significantly infiltrated in control animals, and the mRNA level of CCR2, CCR5, CXCR2, CXCR4, and CX3Crl were augmented in the control animals. Our studies of the effect of monoclonal antibody against CD11b of β2-integrin demonstrated that the antibody modulated the CD11b molecules and prevented the mild, but not severe ischemic renal injury. Together taken in, the molecule of CD11b might be involved in the progression of renal diseases. SUMMARY The present clinical and experimental studies suggested the important role of CD11b of β2-integrin, probably expressed on Mf in progressive renal disease as well as CA rejection.
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[Publications] Tajra, LCF., Martin X., Margonari, J., Blan-Brunat, N., Ishibashi, M., Vivier, G., Steghens, JP, Kawashima, H., Miyasaka, M., Dubernard, JM., Revillard, JP: "Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not major renal ischaemic injury"Nephrol. Dial. Transplant. 15. 1556-1561 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Ishibashi, M., Blanc, M. Wagner, A., Mioskowski, C., Xavier Martin, X., Uemura, H., Shiiki, H., Konishi, N., Dubernard, JP., and Hirao, Y.: "COMBINED USE OF SELECTIVE INHIBITOR OF MACROPHAGE-EFFECTOR GENERATION FOR TREATMENT OF DIFFERENTIAL GLOMERULAR AND TUBULOINTERSTITIAL LESION OF PROGRESSIVE RENAL DISEASES"Abstract of The 35th Annual Meeting of American Society for Nephrology. (2002)
Description
「研究成果報告書概要(欧文)」より
