Complement dependence of antibody-induced mesangial cell injury in the rat.
Complement dependence of antibody-induced mesangial cell injury in the rat.
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DOI：
10.4049/jimmunol.138.11.3758
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发表时间：
1987-06
影响因子：
4.4
通讯作者：
T. Yamamoto;C. Wilson
中科院分区：
文献类型：
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作者：
T. Yamamoto;C. Wilson
兔抗大鼠胸腺细胞血清（ATS）与存在于大鼠系膜细胞上的thy -1样抗原反应，经静脉注射后，大鼠系膜细胞几乎立即（1小时）损伤，随后出现系膜溶解和系膜增生/浸润性病变。为了确定补体在ATS诱导的肾小球病变中的作用，我们给C3被眼镜蛇毒液因子（CVF）耗尽的Lewis大鼠服用ATS。在未给予CVF的大鼠，在ats治疗1小时后，CVF治疗阻止了系膜细胞的退行性改变和肾小球中少量多形核白细胞（PMN /肾小球）的积累（2.67 PMN/肾小球）。此外，CVF可防止第4天的系膜松解和系膜细胞增多。与兔免疫球蛋白G沉积密切相关的ats治疗大鼠系膜中的大鼠C3和晚期补体成分也因CVF治疗而缺失。通过免疫荧光或配对标记放射性同位素技术研究，CVF治疗不影响ATS与肾小球的结合。通过照射或抗i- mn血清治疗白细胞和/或PMN的消耗对诱导急性系膜细胞损伤或系膜溶解病变没有影响。照射确实减少了4天的增生性/浸润性病变。补体耗竭使ATS诱导的热聚集人γ -球蛋白系膜摄取增加正常化（ATS治疗组为655.0 +/- 35.2微克，ATS + cvf治疗组为20.3 +/- 2.9微克/5 × 10(4)个肾小球）；平均值+/- SEM)。CVF治疗后4至5天，肾系膜区出现小的免疫沉积，代表CVF-抗CVF抗体- c3复合物。ATS诱导的大鼠系膜细胞损伤模型是补体依赖性的，至少在一定程度上可能与补体介导的系膜细胞裂解有关。
Intravenous administration of rabbit anti-rat thymocyte serum (ATS) reactive with Thy-1-like antigens present on rat mesangial cells induces almost immediate (1-hr) mesangial cell injury in rats followed by sequential mesangiolytic and mesangial-proliferative/infiltrative lesions. To determine the role of complement in these ATS-induced glomerular lesions, ATS was given to Lewis rats that had been depleted of C3 by cobra venom factor (CVF). CVF treatment prevented the degenerative changes in mesangial cells and accumulation of even the few polymorphonuclear leukocytes (PMN) seen in the glomeruli (2.67 PMN/glomerulus) 1 hr after ATS-treatment in rats not given CVF. In addition, CVF prevented the mesangiolysis and mesangial hypercellularity seen at day 4. Rat C3 and late complement components identified in the mesangial of ATS-treated rats in close association with the deposition of rabbit immunoglobulin G was also absent as a result of CVF treatment. CVF treatment did not affect binding of ATS to glomeruli as studied by immunofluorescence or paired label radioisotope techniques. The depletion of leukocytes and/or PMN by irradiation or treatment with anti-I-MN serum had no effect on the induction of the acute mesangial cell damage or the mesangiolytic lesion. Irradiation did diminish the 4-day proliferative/infiltrative lesion. Complement depletion normalized the ATS-induced increase in mesangial uptake of heat-aggregated human gamma-globulin (655.0 +/- 35.2 micrograms in ATS-treated vs 20.3 +/- 2.9 micrograms/5 X 10(4) glomeruli in ATS plus CVF-treated rats; mean +/- SEM). Small immune deposits present in the mesangial areas of kidneys 4 to 5 days after CVF treatment represented CVF-anti-CVF antibody-C3 complexes. The model of mesangial cell damage induced by ATS in the rat is complement-dependent and may relate, at least in part, to complement-mediated mesangial cell lysis.