| Project/Area Number |
08457073
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAKEYA Motohiro Kumamoto University SCHOOL OF MEDICINE ASSOC.PROF., 医学部, 助教授 (90155052)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKAWA Kazuhisa Kumamoto University SCHOOL OF MEDICINE ASSISTANT, 医学部, 助手 (00244111)
TAKAHASHI Kiyoshi Kumamoto University SCHOOL OF MEDICINE PROF., 医学部, 教授 (70045631)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | MCP-1 / monoclonal antibody / TRPM-3-positive macrophages / lung granulomatosis / nitric oxide / rat collagen arthritis / rat crescentic glomerulonephritis / squamous metaplasia / 間質性肺炎 / 免疫組織化学 / 単球・マックロファージ / TRPM-3陽性マクロファージ / コラーゲン関節炎 / HTLV-1 associated myelopathy / 肉芽腫 |
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| Research Abstract |
Monocyte chemoattractant protein-1 (MCP-1) is one of the most potent chemoattractants for monocytes which belongs to the C-C chemokine group. In this project, we clarified the crucial role of MCP-1 in various pathological conditions in rats.
1.Injection of recombinant rat MCP-1 into rat skin induced infiltration of TRPM-3-positive activated macrophages, whereas ED2-positive resident macrophages did not accumulate to the injection site.
2.In rat models of pulmonary granulomatosis, we confirmed the expression of MCP-1 in the early phase of inflammation. Administration of nitric oxide synthase inhibitors significantly suppressed nitric oxide (NO) production and resulted in marked reduction monocyte/macrophage infiltration as well as in inhibition of MCP-1 production. These data indicate that NO may induce MCP-1 expression in lung granulomatosis.
3.In collagen-induced rat arthritis, both MCP-1 concentration in the joint lavages and MCP-1 mRNA levels in the joint tissues at 2 weeks after the i
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mmunization of collagen. Injection of an anti-rat MCP-1 monoclonal antibody significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30% compared with controls. These results suggest that MCP-1 plays a critical role in the recruitment of monocytes and in the development of rat arthritis.
4.IN crescentic glomeruionephritis in rats, MCP-1 mRAN and proein are paralleled with the infiltration of monocyte/macrophages into glomeruli. MCP-1 mRNA was expressed intensely in the glomeruli 4days after the anti-glomerular basement membrane antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of monocyte/macrophage infiltrating in the glomeruli decreased by 34.7% and proteinuria by 66.4% at day 4. These data suggest that MCP-1 plays a crucial role in the glomerular accumulation of monocyte/macrophages and that the infiltrating monocyte/macrophages cause glomerular injury and increased excretion of protein in the urine. Less
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