| Project/Area Number |
63480189
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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 |
内科学一般
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| Research Institution | NAGOYA UNIVERSITY |
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Principal Investigator |
MATSUO Seiichi NAGOYA UNIVERSITY INTERNAL MEDICINE (III) INSTRUCTOR, 医学部, 助手 (70190410)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Yasuhiko NAGOYA UNIVERSITY INTERNAL MEDICINE (III) FELLOW, 医学部, 医員
YOSHIDA Futoshi AICHI GAKUIN UNIVERSITY DENTISTRY ASSISTANT PROFESSOR, 歯学部, 講師
FUKATSU Atsushi NAGOYA UNIVERSITY INTERNAL MEDICINE (III) FELLOW, 医学部, 医員
WATANABE Yuzo NAGOYA UNIVERSITY INTERNAL MEDICINE (III) INSTRUCTOR, 医学部, 助手 (90135369)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1989: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1988: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | GLOMERULONEPHRITIS / IMMUNE COMPLEX / LECTIN / ENDOTHELIUM / EPITHELIUM / MONOCLONAL ANTIBODY / 細胞骨格 / モノクロ-ナル抗体 / 上皮下沈着物 / 基底膜 |
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| Research Abstract |
(1) Establishment of a new model of experimental glomerulonephritis in rats
A model of experimental glomerulonephritis characterized by the initiation of antibody-antigen reaction on the surface of glomerular endothelium was established by kidney perfusion technique using lectin(s) and its antibodies. The nature of this experimental model was studied precisely by immunohistologic methods.
(2) Mechanisms of the formation of granular immune deposits on the surface of glomerular endothelium immediately after the interaction of antibodies and implanted lectin
Rapid relocalization and formation of granular immune deposits on the surface of glomerular endothelium was thought to be connected to the function of cytoskeleton because granular immune deposit formation was inhibited when experiments were carried out at 4ﾟC, using Fab fraction of antibodies instead of intact IgG molecules, or by the use of chlorpromazine.
(3) Kinetics of immune deposits after the initial event
Immune deposits initially
… More
formed on the surface of glomerular endothelium changed their localization rather rapidly to the subendothelial area, and then to subepithelial area. This fact was explained by the shodding of immune deposits from the surface of endothelium and then by the filtration pressure across the glomerular capillary walls. These observations have relevance to the pathogenesis of human membranous glomerulonephropatliy.
(4) Studies on the mechanisms of the formation of immune deposits on the surface of glomerular cells in culture
Using rat glomerular epithelial cells in culture, immune complexes containing antibodies and foreign antigen planted on the cell surface were shed to the extracellular structure.
(5) Production of monoclonal and polyclonal antibodies reacting with glomerulus and their nephritogenicity
Rabbit antibodies against sialoglycoprotein purified by the HPA-affinity column chromatography were obtained and named RBAHPA-PM. RBAHPA-PM reacted specifically with podocyte free surface and recognized the epitope(s) involving N-glycan. The antigen recognized by RBAHPA-PM was also present in human glomeruli suggesting that this epitope has relevance to certain human glomerulonephritides such as acute poststreptococcus glomerulonephritis. Several monoclonal antibodies were tested in rats and it was demonstrated that these antibodies could induce glomerular injury. Less
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