ROLE OF POLYCATIONIC MEDIATORS IN GLOMERULONEPHRITIS

聚阳离子介质在肾小球肾炎中的作用

• 批准号: 3238231
• 负责人: JEFFREY L BARNES
• 金额: $ 10.86万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3238231
• 关键词: autoimmune disorder; disease /disorder model; electrofocusing; glomerulonephritis; immune complex; immunization; kidney disorder chemotherapy; kidney pharmacology; nephrectomy; neutrophil; platelet activating factor; prostacyclins; renal glomerulus; reptile poison; serum sickness; theophylline

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.

建议进行研究，检查血小板/中性粒细胞 激活和随之而来的肾小球结合释放的 阳离子蛋白引起肾小球通透性改变， 免疫复合物在早期发病机制 肾小球肾炎 研究将使用以下内容 实验模型：首先，炎症细胞将被 通过肾内动脉输注合成的 血小板活化因子（PAF）引起内源性 来自嗜碱性粒细胞的PAF。 随之而来的阳离子蛋白质的影响 将通过测量肾小球渗透性来测试释放， 大分子和预形成的可溶性免疫复合物。 在 第二，将BSA灌注到BSA中的肾动脉中， 免疫兔子 体内形成的免疫复合物将 作为细胞激活和阳离子蛋白的触发器 release. 第三，炎症细胞的生物学 活化、阳离子蛋白结合和免疫复合物 将在兔模型中研究肾小球中的沉积， 急性血清病 药物干预将是 用于钝化炎症细胞活化， 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 前蛋白（肝素），从而试图降低免疫力 复杂的沉积。 此外，一个共同的特点， 肾小球肾炎是细胞过多的发展， 血液传播炎症细胞浸润的结果 和/或固有肾小球细胞的增殖。 研究 被提议研究生物学上的潜在作用 活性血小板阳离子蛋白在募集 炎症细胞对肾小球结构和/或 在免疫和免疫反应中， 进行性肾小球疾病的非免疫模型。 肾小球细胞过多将由以下因素引起：（1）形成 大的肾小球内免疫复合物， 如上所述预免疫兔中的BSA; 消融1和5/6的总肾脏质量， 残肾超滤;（3） 去氧皮质类固醇-盐诱导的高血压;和（4） 静脉注射哈布蛇毒。 治疗 用抗血小板药物噻氯匹定进行干预， 将使用抗血小板血清和肝素来钝化 血小板活化和试图改善肾小球 细胞过多