1992 Fiscal Year Final Research Report Summary
INDUCTION OF AUTOIMMUNE-TYPE LIVER INJURY IN MICE BY THE ANTI-IDEOTYPIC ANTIBODY TO THE ANTI-ASIALOGLYCOPROTEIN RECEPTOR ANTIBODY.
| Project/Area Number |
03670363
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
MIZUNO Motoo OKAYAMA UNIVERSITY HOSPITAL ATTACHED TO MEDICAL SCHOOL, ASSISTANTS, 医学部附属病院, 助手 (90221605)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Monoclonal antibody / Anti-ideotypic antibody / Hepatocyte membrane / Asialoglycoprotein receptor / Autoimmune-type liver injury |
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| Research Abstract |
1.Analysis of 8D7 monoclonal antibody (MoAb).
8D7 monoclonal antibody (MoAb) was shown to react with affinity-purified human asialoglycoprotein receptors (ASGPR) in an ELISA. Distributions of ASGPR in human hepatocellular carcinoma (HCC) was studied immunohistochemically. ASGPR was distributed diffusely on the plasma membrane in the well differentiated HCC. In contrast, the surface expression of ASGPR was lost in poorly differentiated HCC. Various alterations of the expression of ASGPR closely related to differentiation and proliferative activity of the tumor cells were shown in HCC.
2.Production of anti-ideotypic antibodies to the 8D7 anti-ASGPR MoAb.
BALB/c mice were immunized with 8D7 MoAb, and a syngenetic anti-ideotypic (anti-Id) MoAb, 3C8, an IgMkappa, was generated. 3C8 MoAb bound to 8D7 MoAb in an membrane constituents in an ELISA. The liver membrane constituents inhibited 8D7 MoAb binding to 3C8 MoAb in an ELISA. Immunohistochemical staining of the plasma membrane of rat hepatocytes by 8D7 MoAb was inhibited by the 3C8 anti-Id MoAb.
BALB/c mice were immunized with 3C8 anti-Id MoAb, and anti-anti-Id MoAbs which reacted with the liver membrane constituents could be generated. These results suggest that 3C8 anti-Id MoAb recognizes paratope of 8D7 anti-ASGPR MoAb and includes "internal images".
3.Induction of autoimmune-type liver injury by 3C8 anti-Id MoAb.
Thymectomy of BALB/c mice was performed 3 days after birth, and thymectomized mice were immunized with 3C8 anti-Id MoAb. This experiment is currently on going.
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