TRAUMA PRIMES CELLS

多器官功能衰竭(MOF)是迟发性损伤后的主要原因 死亡率。我们认为，细胞对炎症的反应 刺激可受宿主动物先前的伤害或 有耐心的。因此，最初的损伤“启动”细胞表现出 对随后的侮辱做出放大的反应。这种现象是最好的 中性粒细胞的“启动”就是例证。我们假设伤害 “质数”细胞。这种启动可能会放大细胞对 随后以建设性或破坏性的方式进行刺激。 事实上，创伤引发了一场生理保护或生理上的竞赛 破坏性计划，其临床结果由 每一次侮辱的程度和顺序。 这个创伤研究中心由5个独立项目组成，全部 与第一个临床核心项目有关。在临床核心领域，我们 建议量化患者最初受伤的程度。跟随 最初的复苏，我们计划检查高代谢“启动” 患者将确定在此期间是否出现第二次炎症性侮辱 脆弱时期预测MOF(项目1)。高代谢状态 将在动物身上进行调查，以确定炎症性 介体可以敏化(保护)和/或减敏(伤害)β- 肾上腺素能受体偶联的心肌功能(项目2)。胆量 作为财政部发展的核心机构而被援引。我们 损伤后肠系膜缺血/再灌流促进远端 作为循环中性粒细胞“启动”床的器官损伤 (项目3)。 与创伤相关的强烈交感神经刺激可能会“启动” 细胞代谢促进对后续疾病的耐受 缺血性/炎症性侮辱(项目4)。归根结底，细胞被 伤害表达了与保护和保护有关的基因的共同程序 恢复(项目5)。 在我们发展成为创伤研究中心的同时，我们建议 作为创伤研究培训中心发挥作用。

Multiple organ failure (MOF) is the leading cause of late post-injury mortality. We propose that the cellular response to an inflammatory stimulus can be influenced by a prior injury to the host animal or patient. Thus, the initial injury "primes" cells to exhibit an amplified response to a subsequent insult. This phenomenon is best exemplified by the "priming" of neutrophils. We postulate that injury "primes" cells. this priming may amplify the cellular response to a subsequent stimulus in either a constructive or destructive fashion. Indeed, trauma initiates a race between physiologically protective or destructive programs, the clinical result of which is dictated by the magnitude and sequence of each insult. This Trauma Research Center is composed of 5 independent projects all relating to the first clinical core project. In the clinical core, we propose to quantify the magnitude of initial patient injury. Following initial resuscitation, we plan to examine the hypermetabolic "primed" patient to determine whether a second inflammatory insult during this vulnerable period predicts MOF (Project 1). The hypermetabolic state will be investigated in animals to determine whether inflammatory mediators can sensitize (protect) and/or desensitize (injure) beta- adrenergic receptor coupled myocardial function (Project 2). The gut has been invoked as an organ central to the development of MOF. We propose that post-injury mesenteric ischemia/reperfusion promotes remote organ injury by serving as a "priming" bed for circulating neutrophils (Project 3). The intense sympathetic stimulation associated with trauma may "prime" cellular metabolism to promote tolerance to subsequent ischemic/inflammatory insult (Project 4). Ultimately, cells "primed" by injury express a common program of genes which relate to protection and recovery (Project 5). Concurrent with our development as a Trauma Research Center, we propose to function as a Trauma Research Training Center.