PATHOPHYSIOLOGY OF IMMUNE GLOMERULAR INJURY

免疫性肾小球损伤的病理生理学

基本信息

批准号：
3240419
负责人：
CURTIS B WILSON
金额：
$ 17.4万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 1994-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3240419
关键词：
autoimmune disorder cellular immunity disease /disorder model glomerular filtration glomerulonephritis goats hemodynamics humoral immunity immunopathology kidney circulation disorder laboratory rabbit laboratory rat micropuncture pathology renal tubular transport tissue /cell culture

项目摘要

This proposal represents a unique collaboration between the disciplines of renal immunomorphology and glomerular pathophysiology, and is designed to provide new information not otherwise attainable. We will define the individual contributions of antibody reactions and their augmenation by biologically active mediator molecules in the genesis and functional consequences of immune forms of glomerular injury. We will amplify our collaborative studies with a new combined in vivo/in vitro approach using the isolated perfused kidney. Individually, glomerular micropuncture and immunomorphologic analysis of experimental models of glomerular injury, even with selected mediator depletion, provide only partial answers to the quantitative contributions of the various interactive mediator pathways. Mediator infusion into the renal artery offers another avenue; however, the mediator still must be viewed in the context of the circulating humoral and cellular milieu. Glomerular hemodynamic analysis of selective mediator effects in vitro in the isolated perfused kidney will be used to supplement the above techniques and couple them with our immunomorphologic and pathophysiologic findings in vivo. Studies will first establish the glomerular hemodynamics of the isolated perfused kidney to provide information about the mechanism of its decreased filtration fraction. Next, glomerular hemogdynamics of nephritic isolated perfused kidneys and kidneys rendered nephritic by ex vivo treatment will be compared with those in vivo. The effect of biological mediator molecules will be correlated using in vivo renal artery infusion and in vitro isolated perfused kidney infusion to quantitate the selective actions. Studies will then progress to assessing glomerular hemodynamics, immunomorphologic correlates, and mediation of immune and chemical injuries in selected glomerular cell populations. Ongoing studies will continue to define additional features of anti-glomerular basement membrane antibody disease, with particular emphasis on factors influencing glomerular-tubular feedback and oxidant injury. Merging of our individual immunomorphologic and glomerular hemodynamic interest has and will provide an increasingly detailed assessment of the correlates of glomerular pathophysiologic change. The combined in vivo and in vitro approach will define the important elements of the immune mechanisms of glomerular injury and the quantitative contribution of mediator systems amenable to therapeutic manipulation.

该提案代表了肾脏免疫形态和肾小球的学科病理生理学，旨在提供新信息而不是否则可以实现。我们将定义个人贡献抗体反应及其通过生物活性介体分子在起源和功能后果中肾小球损伤的免疫形式。我们将放大我们的合作研究与新的体内组合组合使用孤立的灌注肾脏的方法。单独肾小球微孔和免疫形态学分析肾小球损伤的实验模型，即使选择调解器耗尽，仅提供部分答案各种交互式介体的定量贡献途径。介质输入肾动脉提供了另一种大街;但是，调解员仍然必须在上下文中查看循环的体液和细胞环境。肾小球体外选择性介质作用的血液动力学分析孤立的灌注肾脏将用于补充上述技术并将它们与我们的免疫形态学和体内的病理生理发现。研究将首先建立孤立的灌注肾脏的肾小球血流动力学提供有关其降低机制的信息过滤分数。接下来，肾肾小球的肾小球血压素孤立的灌注肾脏和肾脏由Ex呈肾素体内治疗将与体内进行比较。效果生物介体分子将使用体内相关肾动脉输注和体外孤立的灌注肾脏输注量化选择性动作。然后研究将进展评估肾小球血流动力学，免疫形态学与免疫和化学损伤的相关和介导选定的肾小球细胞群。正在进行的研究将继续定义抗斜体的其他特征地下室膜抗体疾病，特别强调影响肾小球 - 管状反馈和氧化剂的因素受伤。合并我们的个人免疫形态学和肾小球血流动力学的兴趣已经并且将提供对肾小球相关性的越来越详细评估病理生理变化。体内和体外合并方法将定义免疫的重要元素肾小球损伤的机制和定量贡献可容纳治疗操作的调解人系统的。