AUGMENTED INJURY DUE TO AUTOLOGOUS INFLAMMATORY ATTACK

自体炎症发作导致损伤加重

• 批准号: 2392237
• 负责人: FRANCIS D MOORE
• 金额: $ 107.35万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2392237
• 关键词: complement; disease /disorder model; inflammation; injury

This proposal represents a highly integrated examination of the mechanisms by which injured tissue elicits a response from the host and of the harmful effects of this response. Data which from our past study of the complement response pro-inflammatory serum protein system suggests that, in many circumstances, the complement response causes more of an injury than the original insult itself. Accordingly, inhibition of complement has led to a diminution in the degree of final injury. Therefore, we hypothesize that major injury is critically exacerbated by the autologous inflammatory response. We wish to (1) understand the mechanism by which injured tissue activates the inflammatory response, (2) understand the sequence of events leading from the injury's local inflammatory reaction to remote, secondary organ damage, (3) to directly relate the metabolic changes of an injured tissue to the inflammatory attack directed against it, (4) to compare the inflammatory response to injury to the response generated by infectious insults, and (5) synthesize these data to produce an effective therapeutic strategy to reduce the degree of tissue damage which results from a specific injury occurrence. The Trauma Center Core will provide the forum with which to focus the group of five investigators in their examination of the interrelationship of complement with cytokines, adhesion molecules, and tissue metabolism by utilizing shared animal models, assays, facilities, and intellects. Project one ill examine the effect of complement activation o n macrophages and the role of complement in a cytokine-driven model of multiple system organ failure. The second project will relate changes in cellular energetics and membrane metabolism to indicators of inflammatory attack utilizing NMR technology in models of ischemia and reperfusion injury. Project three will assess the interplay of complement and adhesive mediators, as well as defining the state of injured tissues' autoprotective membrane protein apparatus. The fourth project will assess changes in injured tissue membrane proteins and address the problem of specific therapy. A final, shared, aspect of the Trauma Center will be the testing of hypotheses in a series of human observational protocols. By this funding mechanism, we wish to efficiently and by multiple techniques assess the veracity of our primary hypothesis and to postulate therapies more specific than global inhibition of serum complement.

这项建议代表了对这些机制的高度综合审查 受损伤的组织通过它引起宿主和有害组织的反应 这一反应的影响。这些数据来自我们过去对补语的研究 反应促炎血清蛋白系统表明，在许多 在这种情况下，补体反应造成的伤害比 原创侮辱本身。因此，对补体的抑制导致了 最终受伤程度的降低。因此，我们假设 自体炎症严重加重了严重的损伤 回应。我们希望(1)了解损伤组织 激活炎症反应，(2)了解事件的顺序 从损伤的局部炎症反应导致远端继发性 器官损伤，(3)直接与受伤者的代谢变化有关 组织到针对它的炎症攻击，(4)比较 炎性反应对损伤产生的反应由感染性 侮辱，以及(5)合成这些数据以产生有效的治疗 减少组织损伤程度的策略，这种损伤是由 具体的伤害发生。 创伤中心核心中心将提供一个论坛，让团队集中精力 五位调查人员在他们对 补体与细胞因子、黏附分子和组织新陈代谢 利用共享的动物模型、化验、设施和智力。 项目一将检验补体激活对巨噬细胞的影响。 补体在细胞因子驱动的多系统模型中的作用 器官衰竭。第二个项目将涉及细胞内的变化 能量学和膜代谢对炎症发作指标的影响 核磁共振技术在脑缺血再灌注损伤模型中的应用。 项目三将评估补体和粘合剂的相互作用 介体，以及定义损伤组织的自我保护状态 膜蛋白仪。第四个项目将评估 损伤组织膜蛋白与解决特异性问题的关系 心理治疗。创伤中心的最后一个共享方面将是测试 一系列人类观测方案中的假设。 通过这一筹资机制，我们希望通过高效和多次 技术评估我们主要假设和假设的真实性 比全面抑制血清补体更特异的治疗方法。