No complement receptor 1 stumps on podocytes in human glomerulopathies
No complement receptor 1 stumps on podocytes in human glomerulopathies
复制标题
DOI：
10.1046/j.1523-1755.2001.00476.x
复制
发表时间：
2001-01-01
影响因子：
19.6
通讯作者：
Schifferli, JA
中科院分区：
文献类型：
--
作者：
Moll, S;Miot, S;Schifferli, JA
背景1型补体受体（CR 1）是足细胞上补体的唯一生理抑制剂。CR 1在不同的肾小球疾病中丢失，特别是在狼疮性肾炎中，其中已经表明CR 1通过蛋白水解从细胞膜中除去。为了确定CR 1对足细胞的蛋白水解裂解是否是一种普遍现象，我们分析了CR 1在不同肾小球疾病中的表达，使用单克隆抗体对分子的细胞外部分上存在的表位和针对CR 1的细胞内尾部的多克隆抗体。将两种抗体应用于肾活检的连续系列组织切片。在正常肾小球中，这两种抗体提供了相似的结果，即足细胞的强染色，并且两者都显示出特异性识别CR 1。在狼疮性肾炎（8/8）、局灶性节段性肾小球硬化（FSGS; 7/7）、伊加肾炎（6/6）、膜性肾小球肾炎（3/3）和微小病变性疾病（3/3）中观察到CR 1细胞外部分的表达降低。在每种情况下，表达的降低伴随着CR 1细胞内尾部表达的同时降低（斯皮尔曼相关系数r（s）= 0.951，P < 0.001）。这一观察结果通过分析连续切片上的局灶性肾小球病变得到证实。这些数据表明，即使在狼疮性肾炎中，足细胞上也没有CR 1残端，并表明足细胞上的CR 1损失不是由于消耗而是由于合成减少。CR 1合成的丧失可能使足细胞对补体攻击高度敏感。
Background. Type one complement receptor (CR1) is the only physiological inhibitor of complement on podocytes. CR1 is lost in different glomerulopathies, in particular in lupus nephritis, in which it has been suggested that CR1 is removed by proteolysis from the cell membrane.Methods. To define whether proteolytic cleavage of CR1 on podocytes is a general phenomenon, we analyzed the expression of CR1 in different glomerulopathies using a monoclonal antibody against epitopes present on the extracellular portion of the molecule and a polyclonal antibody directed at the intracellular tail of CR1. The two antibodies were applied on sequential serial histologic sections of renal biopsy.Results. In normal glomeruli, the two antibodies provided similar results, that is, strong staining of podocytes, and both were shown to recognize specifically CR1. Decreased expression of the extracellular portion of CR1 was observed in lupus nephritis (8/8), focal and segmental glomerulosclerosis (FSGS; 7/7), IgA nephritis (6/6), membranous glomerulonephritis (3/3), and minimal change disease (3/3). In each case, the decreased expression was accompanied by a simultaneous decrease of the expression of the intracellular tail of CR1 (Spearman's correlation coefficient r(s) = 0.951, P < 0.001). This observation was confirmed by analyzing focal glomerular lesions on sequential serial sections.Conclusion. These data indicate that there are no CR1 stumps on podocytes, even in lupus nephritis, and suggest that the CR1 loss on podocytes is not due to consumption but to decreased synthesis. A loss of CR1 synthesis might render podocytes highly sensitive to complement attack.