THERMAL INJURY, COMPLEMENT AND LEUKOCYTE DYSFUNCTION

热损伤、补体和白细胞功能障碍

• 批准号: 3275766
• 负责人: Peter A Ward
• 金额: $ 15.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-01-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3275766
• 关键词: acquired immunodeficiency; alveolar macrophages; complement inhibitors; complement pathway; disease /disorder model; flow cytometry; free radicals; heat injury; immunoregulation; inflammation; leukocyte activation /transformation; leukocyte depletion therapy; leukocyte disorder; lipid peroxides; neutrophil; phagocytes; platelets; radiotracer; respiratory gas analyzer; tissue /cell culture; vascular endothelium permeability

Our recent studies of skin thermal injury in rats have demonstrated the onset of systemic activation of complement, acquisition of phagocytic cell defects and development of secondary lung injury. The pulmonary complication has been related to intravascular activation of neutrophils, entrapment of leukoaggregates in lungs and the development of pulmonary vascular endothelial injury due to oxygen radical (hydroxyl radical) formation by leukocytes. We now plan to examine both local effects of thermal injury as well as some of the systemic complications (phagocytic cell defects and intravascular hemolysis) arising from localized thermal injury of skin. The proposed studies will focus on mediator systems responsible for the local inflammatory response to thermal injury, the ability of thermally injured parenchymal and mesenchymal cells to activate the complement system, mediators responsible for the acquired defects of phagocytic cells following thermal injury, and the pursuit of preliminary evidence suggesting that intravascular hemolysis associated with thermal injury is probably the combined result of intravascular activation of complement as well as oxygen radical generation by blood neutrophils. The development of flow cytometric techniques to analyze in a quantitative manner unfractionated blood leukocytes from small volumes (0.1 ml) of whole rat blood will greatly facilitate these studies.

我们最近对大鼠皮肤热损伤的研究表明， 补体系统激活开始，吞噬细胞获得 继发性肺损伤的发生和发展。 肺 并发症与中性粒细胞的血管内激活有关， 肺内白细胞聚集体的滞留与肺动脉高压的发生 氧自由基（羟自由基）致血管内皮损伤 由白细胞形成。 我们现在计划研究 热损伤以及一些全身并发症（吞噬细胞 细胞缺陷和血管内溶血） 皮肤损伤。 拟议的研究将集中在中介系统 负责对热损伤的局部炎症反应， 热损伤的实质和间充质细胞活化的能力 补体系统，负责获得性缺陷的介质， 吞噬细胞热损伤后，和追求初步的 有证据表明，与热相关的血管内溶血 损伤可能是血管内激活 补体以及血液中性粒细胞产生氧自由基。 的 流式细胞术技术的发展，以定量分析 从小体积（0.1 ml）的全血中分离未分级的血白细胞 老鼠的血液将极大地促进这些研究。