1998 Fiscal Year Final Research Report Summary
The role of chemokine in human nephritis and basic research of anti-chemokine therapy in experimental nephritis model.
| Project/Area Number |
09671157
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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 |
Kidney internal medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOKOYAMA Hitoshi University Hospital, Kanazawa University Assistant Professor, 医学部・附属病院, 助教授 (50191531)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Glomerulonephritis / IgA nephropathy / Experimental nephritis / Chemokine / IL-8 / MCAF / MCP-1 / Adhesion molecule / Soluble form of adhesion molecule |
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| Research Abstract |
We investigated the pathophysiological roles of a potent macrophage (Mphi) chemokine, monocyte chemotactic and activating factor (MCAF/MCP-1), in a crescentic glomerulonephritis model of Wistar-Kyoto rats. Anti-MCAF/MCP-1 antibodies decreased proteinuria on day 3 and 6, and also decreased the number of Mphi in glomeruli and crescentic formation in nephritic rats. Furthermore, anti-M CAF/MCP- 1 antibodies remarkably reduced glomerulosclerosis and improved renal dysfunction on day 56. The single administration of anti-MCAF/MCP- I antibodies on day 7 decreased necrotizing lesions and increase of proteinuria as compared with control lgG treated rats. These results suggest that MCAF/MCP-1 essentially participates in the impairment of renal functions associated with crescentic glomerulonephritis by both recruitin2 and activating Mphi in the early phase. We also investigated the involvement of chemokines and the expression of adhesion molecules in human nephritis. Urinary and serum MCAF/MCP-1 levels were significantly high in patients with lupus nephritis including WHO lVb/c. in addition, MCAF and IL-S were differentially expressed in kidneys with IgA nephropathy, and their subtypes. P-selectin and IL-8 were expressed in glomeruli of proliferative glomerulonephritis and were correlated with endocapillary proliferation, CD4Ib (activated platelets) and leukocyte infiltration.
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