Barnes J l, Camussi G, Tetta C, Venkatachalam M A
Department of Pathology, University of Texas Health Science Center, San Antonio.
Lab Invest. 1990 Dec;63(6):755-61.
Synthetic polycations bind to glomerular polyanions (GPA) and increase permeability to macromolecules and immune complexes. Platelet factor 4 and other platelet cationic proteins also bind to GPA and may play a role in immune complex deposition. Here we examine the potential of locally released cationic proteins to bind to GPA after immune complex-induced platelet activation within the renal microvasculature. Rabbits were immunized against bovine serum albumin (BSA), and BSA (2 or 4 mg/ml in buffered saline) was infused into the left renal artery to deliver 8 or 16 mg of BSA over 20 minutes. Thirty minutes later, kidneys were removed and tissue processed for light, immunofluorescence, and electron microscopy for the assessment of glomerular alterations and the localization of immune complexes (IgG and BSA), platelet factor 4, and platelet cationic proteins. GPA was measured by quantitative ultrastructural assessment of polyethyleneimine binding sites. Glomerular capillaries contained large intraluminal immune complexes and platelet aggregates. Also, numerous deposits were observed within subendothelial and subepithelial aspects of the glomerular basement membrane (GBM). Immunofluorescence and immunocytochemistry revealed prominent localization of platelet factor 4, platelet cationic proteins, IgG and BSA within peripheral capillary walls of glomeruli concomitant with a reduction in GPA. Glomeruli of controls or contralateral kidneys did not show GBM localization of immune complexes or platelet proteins. Thus, nascent formation of immune complexes in capillaries was associated with platelet activation and deposition of endogenous cationic proteins in the GBM. This mechanism may be involved in neutralization of GPA and mediation of increased permeability, which leads to GBM deposition of immune complexes.
合成聚阳离子与肾小球多阴离子（GPA）结合，增加对大分子和免疫复合物的通透性。血小板因子4和其他血小板阳离子蛋白也与GPA结合，并可能在免疫复合物沉积中起作用。在这里，我们研究了肾微血管内免疫复合物诱导血小板活化后局部释放的阳离子蛋白与GPA结合的潜力。用牛血清白蛋白（BSA）免疫兔子，然后将BSA（在缓冲盐水中浓度为2或4mg/ml）注入左肾动脉，在20分钟内输送8或16mg的BSA。30分钟后，取出肾脏并进行组织处理，用于光镜、免疫荧光和电子显微镜检查，以评估肾小球改变以及免疫复合物（IgG和BSA）、血小板因子4和血小板阳离子蛋白的定位。通过对聚乙烯亚胺结合位点的定量超微结构评估来测量GPA。肾小球毛细血管内含有大量管腔内免疫复合物和血小板聚集体。此外，在肾小球基底膜（GBM）的内皮下和上皮下区域观察到大量沉积物。免疫荧光和免疫细胞化学显示血小板因子4、血小板阳离子蛋白、IgG和BSA在肾小球外周毛细血管壁内显著定位，同时GPA减少。对照或对侧肾脏的肾小球未显示免疫复合物或血小板蛋白在GBM的定位。因此，毛细血管中免疫复合物的新生形成与血小板活化以及内源性阳离子蛋白在GBM中的沉积有关。这种机制可能参与了GPA的中和以及通透性增加的介导，从而导致免疫复合物在GBM沉积。
