ROLE OF CIRCULATING CELLS IN GLOMERULAR INJURY

循环细胞在肾小球损伤中的作用

• 批准号: 3464054
• 负责人: AGNES B. FOGO
• 金额: $ 10.91万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3464054
• 关键词: angiotensin II; arachidonate; biological signal transduction; blood /plasma substitute; cell adhesion; cell membrane; cellular pathology; chemotaxis; dietary lipid; disease /disorder model; endotoxins; essential fatty acids; free radical oxygen; glomerulonephritis; inflammation; kidney cell; kidney circulation; kidney metabolism; laboratory rat; leukocyte activation /transformation; leukocyte oxidative burst; leukotrienes; lipid peroxides; membrane lipids; micropuncture; neutrophil; nutrition related tag; omega 3 fatty acid; renal glomerulus; vascular endothelium; vasoactive agent; vasoconstriction; vasoconstrictors

Acute renal injury, which occurs as a result of a variety of pathogenic insults, leads to a serious immediate derangement in body homeostasis, and also often triggers subsequent progressive deterioration of kidney structure and function. Based on the large volume of studies conducted in this field, it is now clear that the derangements occurring in acute renal injury are the result of abnormalities at numerous sites within the nephron, including renal vessels, glomeruli, tubules and interstitium, all of which may again contain numerous cell types, both resident, circulating and/or infiltrating. Based on data from us and others, the polymorphonuclear leukocyte appears to be pivotal in determining acute renal injury. In this project the PI will investigate mechanisms through which the polymorphonuclear leukocyte (PMN) participates in damage to the glomerulus. Using in vivo rat models, several sets of studies are designed to answer the following questions: 1) What specific role do PMNs have in the glomerular dysfunction expressed in intact systems, and 2) Are these functions modulated by the fatty acid composition of the PMN and/or the resident glomerular cell, and what are the intracellular mechanisms which underlie these modulations, and 3) Do glomerular cells, particularly mesangial cells, play a role in "chemoattraction" of PMNs? A series of closely related experiments with functional and structural assessments of the microcirculation will be conducted to address the above issues. In this regard PI and her associates have recently developed methodology in two areas: One is a micro-infusion technique via a first-order branch of the renal artery, which allows functional and morphological comparison between populations of glomeruli exposed to different experimental conditions within the same kidney. Thus, this technique can provide a previously unattainable sensitivity in detecting subtle biological differences. The other is a "bloodless" rat model (near total exchange transfusion with a modified stroma-free hemoglobin). This allows, by selective repletion, assessment of the role of PMNs in vivo. Moreover, ex vivo experimental manipulations of the PMNs before repletion gives the opportunity to study the specific cellular mechanisms involved in their in vivo pathogenic function. In conjunction with in vitro studies, the projects aim to identify the mechanisms present in PMNs vs. glomerular cells, through which dietary fatty acid manipulation affects the glomerular pathophysiologic process.

急性肾脏损伤是由于多种致病性而导致的 侮辱，导致身体稳态严重危险，以及 也经常会触发随后的肾脏逐渐恶化 结构和功能。 基于大量研究 该领域，现在很明显的是，急性肾脏发生的扰动 受伤是由于多个地点异常的结果 肾单位，包括肾脏容器，肾小球，小管和间质，所有 其中可能再次包含许多居民循环的细胞类型 和/或渗透。 根据我们和其他人的数据， 多形核白细胞似乎在确定急性方面是关键的 肾脏受伤。 在这个项目中，PI将调查机制 多形核白细胞（PMN）参与肾小球的损害。 使用体内大鼠模型，设计了几组研究以回答 以下问题：1）PMN在 在完整系统中表达的肾小球功能障碍，2） 由PMN和/或的脂肪酸组成调节的功能 居民肾小球细胞，什么是细胞内机制 这些调制的基础，以及3）肾小球细胞，特别是 肾小球细胞，在PMN的“趋化吸收”中起作用？ 一系列 与功能和结构评估紧密相关的实验 将进行微循环以解决上述问题。 在 这方面的Pi和她的同事最近开发了 两个领域：一个是通过一阶分支 肾动脉，允许功能和形态学比较 在暴露于不同实验的肾小球种群之间 在同一肾脏内的情况。 因此，该技术可以提供 以前在检测微妙的生物学方面无法实现的灵敏度 差异。 另一个是“无血”大鼠模型（近总交换 无修饰的无基质血红蛋白输血）。 这允许 选择性递送，评估PMN在体内的作用。 而且，前 补充前PMN的体内实验操作给出了 研究其在其中涉及的特定细胞机制的机会 体内致病功能。 结合体外研究 项目旨在确定PMN中存在的机制与肾小球 细胞，饮食脂肪酸操纵会影响肾小球 病理生理过程。