| 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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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | monoclonal antibody / proteinuria / glomerulosclerosis / mechanism of chronic progression / 単クロ-ン抗体 / 補体 |
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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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