Kawamura O
Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1994 Feb;36(2):103-12.
The involvement of adhesion molecules in the accumulation of inflammatory cells in the glomeruli and subsequent glomerular injury was examined in accelerated-type anti-GBM nephritis in rats. This animal model is known to be manifested by progressive and irreversible glomerular damage with rapid influx of monocytes/macrophages into the glomeruli. Up-regulated expression of intercellular adhesion molecule-1 (ICAM-1) was observed exclusively in the glomerular endothelial cells in this model. Therefore we examined the effect of ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) in the pathogenesis of this nephritis. Four groups of rats with accelerated-type anti-GBM nephritis were investigated. The first group was the control group injected with normal mouse IgG 2mg/Kg. The second group was administered mouse anti-rat ICAM-1 monoclonal antibody (1A-29) 2 mg/Kg. The third group was administered mouse anti-rat LFA-1 beta monoclonal antibody (WT-3) 2mg/Kg. The fourth group received both 1A-29 1mg and WT-3 1mg/Kg. Proteinuria and the influx of monocytes/macrophage in this model were decreased after the administration of 1A-29 or WT-3. Simultaneous administration of both antibodies showed intense suppression of the proteinuria and marked reduction of the infiltrating cells. These results suggested that the ICAM-1/LFA-1 pathway is critically involved in the pathogenesis of accelerated-type anti-GBM nephritis in rats.
在大鼠加速型抗肾小球基底膜（GBM）肾炎中，研究了黏附分子在肾小球内炎性细胞积聚及随后的肾小球损伤中的作用。已知该动物模型表现为进行性且不可逆的肾小球损伤，单核细胞/巨噬细胞迅速流入肾小球。在该模型中，仅在肾小球内皮细胞中观察到细胞间黏附分子-1（ICAM-1）表达上调。因此，我们研究了ICAM-1和淋巴细胞功能相关抗原-1（LFA-1）在该肾炎发病机制中的作用。对四组加速型抗GBM肾炎大鼠进行了研究。第一组为对照组，注射2mg/Kg正常小鼠IgG。第二组给予2mg/Kg小鼠抗大鼠ICAM-1单克隆抗体（1A-29）。第三组给予2mg/Kg小鼠抗大鼠LFA-1β单克隆抗体（WT-3）。第四组接受1mg 1A-29和1mg/Kg WT-3。给予1A-29或WT-3后，该模型中的蛋白尿和单核细胞/巨噬细胞流入减少。同时给予两种抗体显示出对蛋白尿的强烈抑制和浸润细胞的显著减少。这些结果表明，ICAM-1/LFA-1途径在大鼠加速型抗GBM肾炎的发病机制中起关键作用。
