| Project/Area Number |
09672254
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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 |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
OHSAWA Motoyasu Teikyo University, Faculty of Pharmaceut.Sci.Professor, 薬学部, 教授 (30129978)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kazuko Teikyo University, Faculty of Pharmaceut.Sci.Res.Assoc., 薬学部, 助手 (90163245)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | autoantibody / polyclonal B cell activation / cadmium / MHC-II |
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| Research Abstract |
Toxic and therapeutic agent-induced autoimmune diseases such as autoimmune-mediated nephritis and dermatitis can be associated with production of autoantibodies, however their mechanisms are not known. Heavy metals like cadmium (Cd) and mercury cause polyclonal B cell activation (PBA) accompanied with autoantibody production. This research project is undertaken to study the mechanism of Cd-induced PBA with special reference to MHC-IT molecules required for T-B cell interaction. By use of cultured spleen cells from BALB/c mice, a role and expresion level of Ia antigen, that is mouse MHC-II, were investigated at Cd induction of PBA.Results are as follows :
1. Effects of anti-Ia antibody on Cd-induction of PBA : Treatment with antibodies against some surface antigens of lymphocytes showed that anti-Ia most sensitively inhibited the induced of PBA.Time course study of anti-Ia for inhibition of Cd-induced PBA showed moreover that Ia antigen expression within 24 hours after Cd addition was necessary to the PBA.
2. Flow cytometric analysis of Ia expression level at Cd-induced PBA : Variations of immune cell populations and Ia antigen expression level in cultured spleen cells treated with Cd were analyzed by flow cytometry. Expression level of Ta antigen after Cd treatmentn was increased with B lymphocyte population in cultured cells. Most of Ia was expressed on B lymphocytes. Ratio of Ia-positive B lymphocytes and cell density of Ia molecules were increased at 24 hours after Cd addition.
These findings indicate that modified Ia antigen expression, in particular enhancement and timing of the expression, is critical for Cd-induced PBA.It is also suggested that MHC-IT molecules i.e. Ia molecules can cause PBA by promoted T-B cell interaction via the molecule expression modified by Cd at early stage of antibody production.
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