1992 Fiscal Year Final Research Report Summary
Analysis of the mechanism of renal injury at molecular levels by application of monoclonal antibodies
| Project/Area Number |
03454168
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Niigata University |
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Principal Investigator |
SHIMIZU Fujio Niigata Univ.Sch.Med. Professor, 医学部, 教授 (40012728)
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| Co-Investigator(Kenkyū-buntansha) |
OITE Takashi Niigata Univ.Sch.Med. Associate Professor, 医学部, 助教授 (60018744)
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| Project Period (FY) |
1991 – 1992
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| Keywords | monoclonal antibody / proteinuria / glomerulosclerosis / mechanism of chronic progression |
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| Research Abstract |
Both proteinuria-inducing monoclonal antibodies (mAb) 1-22-3 and 5-1-6 are very valuable tools for analyzing the mechanism of renal injury at the molecular or epitope levels. These mAbs could induce renal lesions with extraordinary small amounts, much smaller than the previously reported minimum dose in the various experimental glomerulonephritides. Such a small amount of mAb to induce proteinuria, suggests that the recognized antigen must be limited to a critical site important in regulating the permeability of the glomerular capillary wall.
In order to purify the corresponding antigen, isolated glomeruli have been labeled with 125-I by Bolton-Hunter method. Combined with gene cloning characterization of the corresponding antigen is now in progress.
Not Fab but F(ab)2 as well as whole molecule of 5-1-6 could induce proteinuria. Cross-linking of the antigenic molecules on the glomerular epithelial cell surface followed by endocytosis seems to be the process, which is necessary for induction of proteinuria. Such a kinetics was investigated in vitro using isolated glomeruli by applying the various chemical agents, such as NaN3, Cyto- chalasin B or Ca-ionophore. Thus this process was demonstrated to be energy- dependent. Details will be examined further also on the signal transduction system leading to proteinuria.
We have succeeded in inducing irreversible mesangial sclerotic changes with persistent proteinuria by a second injection of mAb 1-22-3 at two weeks after the first injection. It is a very valuable model for investigating the mechanism of chronic progression of human mesangial proliferative glomerulonephritis.
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Research Products
(40 results)
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[Publications] Kawachi,H., Matsui,K., Orikasa,M., Morioka,T., Oite,T. and Shimizu,F: "Quantitative studies of monoclonal antibody 5-1-6 induced proteinuric state in rats" Clin.exp.Immunol.87. 215-219 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okasora,T., Takikawa,T., Utsunomiya,Y., Senoh,L., Hayashibara,H. Shiraki,K., Kasagai,T. and Shimizu,F: "Suppressive effect of superoxide dismutase on adriamycin nephropathy." Nephron. 60. 199-203 (1992)
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「研究成果報告書概要(欧文)」より
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[Publications] Kawachi,H., Orikasa,M., Matsui,K., Iwanaga,T., Toyabe,S., Oite,T and Shimizu,F: "Epitope-specific induction of mesangial lesions with proteinuria by a MoAb against mesangial cell surface." Cline.exp.Immunol.88. 399-404 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kagami,S., Okada,K., Funai,M., Matui,K., Oite,T., Kawachi,H., Shimizu,F. and Kuroda,Y.: "A monoclonal antibody (1G10) recognizes a novel human mesangial antigen." Kidney Int. 42. 700-709 (1992)
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「研究成果報告書概要(欧文)」より
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[Publications] Sato,T., Kawachi,H., Morioka,T., Takashima,N., Saeki,T., Oite,T. Sato,N.l., Takeuchi,M. and Shimizu,F: "Nephrotoxic serum nephritis in nude rats: the roles of host immune reactions in the accelerated type" Clin.exp.Immunol. 91. 131-134 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Takashima,N., Kawachi,H., Oite,T., Nishi,S., Arakawa,M. and Shimizu,F: "Effect of chlorpromazine on kinetics of injected monoclonal antibody in Mo-Ab-induced glomerular injury." Cline.exp.Immunol.91. 135-140 (1993)
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「研究成果報告書概要(欧文)」より
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