AUGMENTED INJURY DUE TO AUTOLOGOUS INFLAMMATORY ATTACK

自体炎症发作导致损伤加重

• 批准号: 6181147
• 负责人: FRANCIS D MOORE
• 金额: $ 114.27万
• 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 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6181147
• 关键词: complement; inflammation; injury

This proposal represents a highly integrated examination of the mechanisms by which injured tissue elicits a response from the host and one of the harmful effects of this response. Data which from our past study of the complement pro-inflammatory serum protein system suggests that, in many circumstances, the complement responses 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 injured tissue to the inflammatory attack directed against it, (4) to compare the inflammatory response to injury to the response generated by other 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 four investigators in their examination of the interrelationship of complement with antibodies and tissue metabolism. by utilizing shared animal models, assays, facilities, and intellects. Project one 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 two will assess the interplay of serum complement and lymphocyte natural antibody repertoire in the production of post-injury inflammation. The third project will investigate both novel methods of complement inhibition and the interaction of local injury with remote injury. The fourth project will assess changes in injured tissue membrane proteins with a goal of antibody based therapy. 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.

这项建议是对各种机制的高度综合审查 通过这种方式，受伤的组织激发了宿主的反应， 这种反应的有害影响。从我们过去的研究数据来看 补体促炎血清蛋白系统表明，在许多 在这种情况下，补体反应比补体反应引起更多的损伤。 原始的侮辱。因此，补体的抑制已经导致 最终损伤程度的降低。因此，我们假设 严重的损伤会因自体炎性反应而严重恶化， 反应我们希望（1）了解受损组织 激活炎症反应，（2）了解事件的顺序 从受伤的局部损伤组织到炎症发作 针对它，（4）比较损伤的炎症反应 其他侮辱产生的反应，以及（5）综合这些数据 制定有效的治疗策略， 由特定损伤事件导致的组织损伤。 创伤中心核心将提供一个论坛， 一个由四名调查员组成的小组， 抗体和组织代谢的影响。通过利用共享 动物模型、测定、设备和试验。项目一将涉及 细胞能量学和膜代谢的变化， 在缺血模型中利用NMR技术的炎症攻击， 再灌注损伤第二个项目将评估血清 补体和淋巴细胞天然抗体库在生产 损伤后炎症。第三个项目将调查这两个小说 补体抑制的方法和局部损伤与补体的相互作用 远程伤害第四个项目将评估受伤组织的变化 膜蛋白与抗体为基础的治疗目标。 通过这种资助机制，我们希望高效地、多方面地 技术评估我们主要假设的准确性并假设 比血清补体的全面抑制更特异的疗法。