ROLE OF POLYCATIONIC MEDIATORS IN GLOMERULONEPHRITIS

我们已经证明合成的聚阳离子与肾小球聚阴离子结合， 改变对大分子和免疫复合物的渗透性。 研究是 建议检查血小板/中性粒细胞活化以及随后的 释放的阳离子蛋白质的肾小球结合引起肾小球改变， 免疫复合物的渗透性在早期发病过程中 肾小球肾炎 这些研究将利用以下实验模型：首先， 炎性细胞将通过肾内动脉输注 致敏“IgE”中合成血小板活化因子（PAF）或抗原 家兔体内嗜碱性粒细胞释放内源性PAF。 的影响 随后的阳离子蛋白质释放将通过测量肾小球 对大分子和预先形成的可溶性免疫复合物的渗透性。 在 第二种方法是将BSA免疫小鼠的肾动脉内灌注BSA， 家兔 体内形成的免疫复合物将作为细胞免疫的触发剂。 活化和阳离子蛋白释放。 第三，生物学 炎性细胞活化、阳离子蛋白结合和免疫复合物 将在兔急性血清 生病了 将采用药物干预来钝化 炎性细胞活化（通过前列环素-茶碱、噻氯匹定或 抗血小板/抗神经炎血清）或中和阳离子蛋白（通过 肝素），从而试图减少免疫复合物沉积。 的 重点是导致免疫复合物沉积的事件，而不是 随后肾小球炎症的明确表征机制， 损害

We have shown that synthetic polycations bind to glomerular polyanion and alter permeability to macromolecules and immune complexes. Studies are proposed to examine if platelet/neutrophil activation and the consequent glomerular binding of released cationic proteins cause altered glomerular permeability to immune complexes during the early pathogenesis of glomerulonephritis. The studies will utilize the following experimental models: In the first, inflammatory cells will be activated by intrarenal arterial infusions of synthetic platelet-activating factor (PAF) or antigen in sensitized "IgE rabbits" to cause release of endogenous PAF from basophils. The effects of ensuing cationic protein release will be tested by measuring glomerular permeability to macromolecules and pre-formed soluble immune complexes. In the second, BSA will be infused into the renal arteries in BSA immunized rabbits. The immune complexes formed in vivo will act as triggers for cell activation and cationic protein release. In the third, the biology of inflammatory cell activation, cationic protein binding and immune complex deposition in glomeruli will be studied in the rabbit model of acute serum sickness. Pharmacologic interventions will be employed to blunt inflammatory cell activation (by prostacyclin-theophylline, ticlopidine, or anti-platelet/antineutrophil sera) or neutralize cationic proteins (by heparins) and thus attempt to decrease immune complex deposition. The emphasis is on events which lead to immune complex deposition and not on the well-characterized mechanisms of subsequent glomerular inflammation and damage.