ROLE OF POLYCATIONIC MEDIATORS GLOMERULOJNEPHRITIS

建议进行研究以检查血小板/中性粒细胞 释放的蛋白的激活及其与肾小球的结合 阳离子蛋白导致肾小球通透性改变 免疫复合物在慢性粒细胞白血病早期发病中的作用 肾小球肾炎。这些研究将利用以下内容 实验模型：首先，炎性细胞将 由肾动脉内注入合成的 血小板活化因子(PAF)引起内源性激素释放 来自嗜碱性细胞的PAF。随后的阳离子蛋白的作用 将通过测量肾小球通透性来测试释放 大分子和预先形成的可溶免疫复合体。在 第二，BSA将被注入肾动脉 免疫的兔子。体内形成的免疫复合体将 作为细胞激活和阳离子蛋白的触发物 放手。第三，炎性细胞的生物学 活化、阳离子蛋白结合与免疫复合体 肾小球中的沉积将在兔模型中进行研究。 急性血清病。药物干预将是 用来钝化炎症细胞的激活，通过 前列环素-茶碱、噻氯匹定或 抗血小板/抗中性粒细胞血清或中和阳离子 原蛋白(通过肝素)，从而试图降低免疫力 复杂的证词。此外，还有一个共同的特点 肾小球肾炎是肾小球细胞增多症的发展 血源性炎症细胞渗出的结果 和/或常驻肾小球细胞的增殖。研究 被提议用来研究生物学上的潜在作用 活性血小板阳离子蛋白在血管紧张素转换酶的募集中的作用 炎症细胞向肾小球结构和/或 免疫和慢性肾小球疾病中肾小球细胞的增殖 进行性肾小球疾病的非免疫模型。 肾小球细胞增多症的诱因有：(1)形成 大的肾小球内免疫复合体和通过输注 免疫前兔的BSA；(2)外科手术 切除肾总肿块的1/6和5/6导致 残肾超滤；(3) 脱氧皮质醇-盐性高血压；和(4) 静脉注射哈布蛇毒。治疗性的 抗血小板药物噻氯匹定的干预， 将使用抗血小板血清和肝素钝化 血小板活化与改善肾小球功能的尝试 细胞增多症。

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) 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/anti-neutrophil sera or neutralize cationic preoteins (by heparins) and thus attempt to decrease immune complex deposition. In addition, a common feature of glomerulonephritis is the development of hypercellularity as the result of infiltration of blood-borne inflammatory cells and/or the proliferation of resident glomerular cells. Studies are proposed to examine the potential roles of biologically active platelet cationic proteins in the recruitment of inflammatory cells to glomerular structures and/or the proliferation of resident glomerular cells in immune and non-immune models of progressive glomerular disease. Glomerular hypercellularity will be induced by: (1) Formation of large intraglomerular immune complexes and by infusion of BSA in preimmunized rabbit as outlined above; (2) Surgical ablation of 1 and 5/6 of the total renal mass leading to hyperfiltration of the remnant kidney; (3) Desoxycorticosterose-salt induced hypertension; and (4) Intravenous administration of Habu snake venom. Therapeutic interventions with the anti-platelet drug ticlopidine, anti-platelet serum and heparin will be employed to blunt platelet activation and attempt to ameliorate glomerular hypercellularity.