1）抗基底膜型糸球体腎炎の新しいモデル（シンポジウム 糸球体腎炎をめぐる最近の話題, 第539回新潟医学会）

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  • A New Anti－Glomerular Basement Membrane Glomerulonephritis Model

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A prototype of anti－glomerular basement membrane （GBM）：nephritis is induced by administrating rabbit anti－rat GBM antibody in rats. Glomerulonerphritis occurs within minutes after binding of the antibody to GBM, followed by fixation of complement and accumulation of polymorphonuclear leukocytes and monocytes/macrophages. In contrast to the prototype of anti－GBM nephritis, a novel type was evoked a few days after anti－GBM antibody of smaller dose was given in Wistar Kyoto （WKY） rats. The model is characterized by glomerular accumulation of CD 8－positive lymphocytes and monocytes/macrophages, crescent formation and critical renal insufficiency. Lnterestingly the anti－GBM nephritis is almost completely suppressed in CD 8－positive lymphocyte－depleted WKY rats, indicating a crucial role of. the lymphoocytes in the induction. The glomerular accumulation of CD 8－positive lymphocytes and monocytes/macrophages is mediated by ICAM－1－B 1 integrin interaction and chemokines such as MCP－1. The CD 8－positive lymphocytes express a B T cell receptor and perforin/granzyme B, indicating that they are cytotoxic T cells and injure glomerular cells through release of perforin/granzyme B. These results strongly suggest that cellular immunity is involved in mediation of the novel anti－GBM nephritis model in WKY rats even though anti－GBM antibody is the trigger. A possible involvement of cellular immunity in human glomerulonephritis should be examined in the future.

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