Fc dependence of macrophage accumulation and subsequent injury in experimental glomerulonephritis.
Fc dependence of macrophage accumulation and subsequent injury in experimental glomerulonephritis.
复制标题
实验性肾小球肾炎中巨噬细胞积累和随后损伤的 Fc 依赖性。
DOI：
10.4049/jimmunol.130.2.735
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发表时间：
1983
影响因子：
4.4
通讯作者：
S. Holdsworth
中科院分区：
文献类型：
--
作者：
S. Holdsworth
在兔子中诱导了 IgG 启动、巨噬细胞介导的实验性肾小球肾炎模型。实验旨在确定这种疾病引发 IgG 抗体的 Fc 部分在诱导巨噬细胞积聚以及随后的蛋白尿和组织学损伤中的重要性。该模型是抗肾小球基底膜抗体诱导的肾小球肾炎自体相的被动模型。用氮芥去除白细胞可防止蛋白尿、巨噬细胞积聚和组织学损伤的发生，但用眼镜蛇毒去补体则没有效果，证实了该模型中损伤的白细胞依赖性但补体独立性。比较了完整疾病起始 IgG 和该相同抗体的 F(ab')2 级分的等摩尔肾脏结合量的影响。完整的 IgG 沉积与大量蛋白尿相关（630 毫克/24 小时，平均值 +/- 106 SD）。出现弥漫性毛细血管内增生性肾小球肾炎，伴有显着的巨噬细胞积聚（54+/-21个巨噬细胞/肾小球）。 F(ab')2 组分的沉积仅与极少量的蛋白尿（28 +/- 7 毫克/24 小时）相关。组织学表现显示没有明显的肾小球肾炎，并且巨噬细胞积聚（4.1+/-0.6巨噬细胞/肾小球）基本上被阻止。因此，该模型中巨噬细胞的积累和随后的损伤取决于疾病起始 IgG 分子的 Fc 部分。这些数据表明免疫粘附是抗体引发的肾小球肾炎中巨噬细胞积累的重要机制。此外，防止 Fc 依赖性巨噬细胞积累并同时消除损伤表明损伤是由巨噬细胞介导的。
An IgG-initiated, macrophage-mediated model of experimental glomerulonephritis was induced in rabbits. Experiments were designed to determine the importance of the Fc portion of this disease-initiating IgG antibody in inducing macrophage accumulation and subsequent proteinuria and histologic injury. The model was a passive model of the autologous phase of anti-glomerular basement membrane antibody-induced glomerulonephritis. Leukocyte depletion with nitrogen mustard prevented the development of proteinuria, macrophage accumulation, and histologic injury, but decomplementation with cobra venom had no effect, confirming leukocyte dependence but complement independence of injury in this model. The effect of equimolar kidney binding quantities of the intact disease-initiating IgG and an F(ab')2 fraction of this same antibody were compared. Intact IgG deposition was associated with heavy proteinuria (630 mg/24 hr, mean +/- 106 SD). A diffuse endocapillary proliferative glomerulonephritis with prominent macrophage accumulation (54 +/- 21 macrophages/glomerulus) developed. Deposition of the F(ab')2 fraction was associated with only minimal proteinuria (28 +/- 7 mg/24 hr). Histologic appearances showed no significant glomerulonephritis, and macrophage accumulation (4.1 +/- 0.6 macrophages/glomerulus) was substantially prevented. Thus, macrophage accumulation and subsequent injury in this model are dependent on the Fc portion of the disease-initiating IgG molecule. These data suggest immune adherence is an important mechanism for macrophage accumulation in antibody-initiated glomerulonephritis. Furthermore, the prevention of the Fc-dependent macrophage accumulation and simultaneous abrogation of injury suggest the lesion is mediated by macrophages.