ABROGATION OF MACROPHAGE-DEPENDENT INJURY IN EXPERIMENTAL GLOMERULONEPHRITIS IN THE RABBIT - USE OF AN ANTIMACROPHAGE SERUM
ABROGATION OF MACROPHAGE-DEPENDENT INJURY IN EXPERIMENTAL GLOMERULONEPHRITIS IN THE RABBIT - USE OF AN ANTIMACROPHAGE SERUM
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DOI：
10.1172/jci110304
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发表时间：
1981-01-01
影响因子：
15.9
通讯作者：
WILSON, CB
中科院分区：
文献类型：
--
作者：
HOLDSWORTH, SR;NEALE, TJ;WILSON, CB
通过使用肾小球细胞培养和形态学技术，显示巨噬细胞大量存在于患有急性血清病（AcSS）的兔子的肾小球内以及抗肾小球基底膜（GBM）抗体诱导的肾小球肾炎（PAGBMN）的自体相被动模型中。为了确定这些细胞在肾小球损伤中所起的作用，用绵羊抗兔巨噬细胞血清（AMS）或正常绵羊血清（NSS）治疗动物。 NSS 给药对两种肾小球肾炎模型的形成均没有影响。在两种模型中，AMS 的使用减少了循环单核细胞的数量，并阻止了巨噬细胞在肾小球内的积累（AcSS/NSS，平均值 126/肾小球，范围 40-251；AcSS/AMS，平均值 8，范围 1-44；PAGBMN/NSS，平均值 52，范围 27-69；PAGBMN/AMS，平均值 5，范围 2-7）。 AMS 治疗的兔子只有轻微的组织学病变，蛋白尿显着减少（AcSS/NSS，平均值 516 mg/24 小时，范围 200-991；AcSS/AMS，平均值 41，范围 3-161；PAGBMN/NSS，平均值 335，范围 55-975；PAGBMN/AMS，平均值 10，范围 2-24）。在由相同的抗 GBM 抗体诱导的肾小球损伤的异源期中进行的类似研究表明，AMS 对这种多形核白细胞相关的损伤期没有影响，证明了抗血清的选择性。在任一模型中，用眼镜蛇毒因子消耗补体并不影响肾小球肾炎的发展，也不影响巨噬细胞的积累。抑制巨噬细胞积聚可以在很大程度上预防这些形式的实验性肾小球肾炎，从而表明巨噬细胞是肾小球损伤和随之而来的蛋白尿的介质。
Macrophages were shown by the use of glomerular cell culture and morphologic techniques to be present in large numbers within the glomeruli of rabbits with acute serum sickness (AcSS) and in a passive model of the autologous phase of antiglomerular basement membrane (GBM) antibody-induced glomerulonephritis (PAGBMN). To determine the part played by these cells in the glomerular injury, animals were treated with a sheep anti-rabbit macrophage serum (AMS) or normal sheep serum (NSS). NSS administration had no effect on the development of either model of glomerulonephritis. The use of AMS reduced the number of circulating monocytes and prevented the accumulation of macrophages within glomeruli in both models (AcSS/NSS, mean 126/glomerulus, range 40-251; AcSS/AMS, mean 8, range 1-44; PAGBMN/NSS, mean 52, range 27-69; PAGBMN/AMS, mean 5, range 2-7). The AMS-treated rabbits had only a minor histologic lesion and profound reduction in proteinuria (AcSS/NSS, mean 516 mg/24 h, range 200-991; AcSS/AMS, mean 41, range 3-161; PAGBMN/NSS, mean 335, range 55-975; PAGBMN/AMS, mean 10, range 2-24). Similar studies in the heterologous phase of glomerular injury induced by the same anti-GBM antibody revealed no effect of the AMS on this polymorphonuclear leukocyte-related phase of injury, demonstrating the selectivity of the antisera. Complement depletion with cobra venom factor did not affect the development of glomerulonephritis nor the accumulation of macrophages in either model. Inhibition of macrophage accumulation can largely prevent these forms of experimental glomerulonephritis, thereby implicating macrophages as mediators of glomerular injury and consequent proteinuria.