Schulze M, Pruchno C J, Burns M, Baker P J, Johnson R J, Couser W G
Division of Nephrology, University of Washington, Seattle 98195.
Am J Pathol. 1993 Jan;142(1):179-87.
In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation.
在抗体介导的肾小球疾病中，C3（C3b）沉积很常见，并被I因子降解为C3c和C3d。然而，肾小球肾炎中C3b降解的动力学尚未明确。为此，我们研究了三种已形成C3沉积的补体依赖性肾小球肾炎模型（被动型海曼肾炎、阳离子化免疫球蛋白G膜性肾病和刀豆球蛋白A-抗刀豆球蛋白A肾小球肾炎）。通过给予眼镜蛇毒因子来阻止C3b沉积，并用特异性抗体和定量荧光密度测定法测量肾小球中C3c和C3d的消失情况。结果显示，在所有三种模型中，C3c沉积在24小时内减少了85%以上。C3c的清除不受沉积物形成部位或机制的影响。尽管缺乏持续的补体激活，C3d沉积仍持续存在。在被动型海曼肾炎中，当通过尿C5b-9排泄监测疾病活动时，C3c的清除与尿C5b-9排泄恢复到正常水平同步。我们得出结论，补体激活停止后24小时内，肾小球中的C3c沉积物会被清除。利用针对C3c部分的特异性抗体对C3进行阳性染色，证明了近期的补体激活，这通常反映了新的免疫沉积物形成。
