Camussi G, Pawlowski I, Saunders R, Brentjens J, Andres G
J Lab Clin Med. 1987 Aug;110(2):196-206.
Experiments were designed to test the effect of a receptor antagonist of platelet activating factor (PAF), SRI63072, on inflammatory injury induced by in situ formation of immune complexes in two vascular districts of the rat that have different structural and hemodynamic characteristics: unilateral glomerulonephritis induced by perfusion of the left kidney of preimmunized animals with cationic human IgG, and passive reversed Arthus reaction in the skin. Three days after perfusion the left kidneys of rats not treated with SRI63072 (group I) were greatly enlarged, and pale and severe exudative and proliferative lesions were present in glomeruli. Granular deposits of human IgG, rat IgG, and rat C3 were seen by immunofluorescence microscopy, and subepithelial electron-dense deposits were visualized by electron microscopy. The right kidneys were consistently normal. The animals were severely proteinuric and had increased levels of PAF in the circulation. In contrast, rats treated with SRI63072 (group II) and studied at the same interval of time developed only mild, focal glomerulonephritis in the perfused kidneys. By immunofluorescence microscopy the glomerular deposits of human IgG and rat IgG were similar in quantity and distribution to those observed in rats of group I. Despite the fact that SRI63072 did not influence the level or the activity of the rat serum complement system, the deposits of C3 were less abundant and more focal. As in animals of group I, electron-dense deposits were present at the epithelial side of the glomerular basement membrane. Proteinuria was slight, and levels of circulating PAF were not significantly increased. These effects cannot be ascribed to interference of SRI63072 with antigen "implantation," antibody binding, or local hemodynamic conditions, because the amounts of glomerular human and rat IgG were the same in treated and untreated rats; SRI63072 did not decrease the glomerular filtration rate; and SRI63072 prevented the increase in vascular permeability and the exudative lesions in passive Arthus reaction in the skin, a model less affected by hemodynamic changes than glomerulonephritis. The beneficial effect of SRI63072 indicates that PAF is an important mediator of the inflammatory process generated either in glomeruli or in the skin by in situ immune complex formation.
实验旨在测试血小板活化因子（PAF）受体拮抗剂SRI63072对大鼠两个具有不同结构和血流动力学特征的血管区域中免疫复合物原位形成所诱导的炎症损伤的影响：用阳离子人IgG灌注预先免疫动物的左肾诱导的单侧肾小球肾炎，以及皮肤中的被动反向Arthus反应。在灌注后三天，未用SRI63072治疗的大鼠（第一组）的左肾明显肿大，肾小球出现苍白以及严重的渗出和增殖性病变。通过免疫荧光显微镜观察到人类IgG、大鼠IgG和大鼠C3的颗粒状沉积物，通过电子显微镜观察到上皮下电子致密沉积物。右肾始终正常。这些动物出现严重蛋白尿，循环中PAF水平升高。相比之下，用SRI63072治疗并在相同时间间隔进行研究的大鼠（第二组），其灌注肾脏仅出现轻度局灶性肾小球肾炎。通过免疫荧光显微镜观察，人类IgG和大鼠IgG在肾小球中的沉积物在数量和分布上与第一组大鼠中观察到的相似。尽管SRI63072不影响大鼠血清补体系统的水平或活性，但C3沉积物较少且更局限。与第一组动物一样，电子致密沉积物存在于肾小球基底膜的上皮侧。蛋白尿轻微，循环中PAF水平没有显著升高。这些作用不能归因于SRI63072对抗原“植入”、抗体结合或局部血流动力学状况的干扰，因为在治疗和未治疗的大鼠中，肾小球中人类和大鼠IgG的量相同；SRI63072没有降低肾小球滤过率；并且SRI63072预防了皮肤被动Arthus反应中血管通透性增加和渗出性病变，皮肤被动Arthus反应模型比肾小球肾炎受血流动力学变化影响小。SRI63072的有益作用表明，PAF是原位免疫复合物形成在肾小球或皮肤中产生的炎症过程的重要介质。
