Overall Application: Trauma Primes Cells

描述（由申请人提供）：我们的总体假设是，人类核心（包含临床数据库和患者样本）与炎症信号传导机制研究之间的双向交流将有助于我们设计创伤致敏细胞的治疗方法。自1993年首次资助以来，我们的MOF数据库已大幅增长，对（I）出血性休克，（II），输血（III），抗炎复苏机制等固有的基本问题产生了新的见解。这些项目仍然高度依赖彼此，并邀请人类核心进一步测试假设。项目我的重点是肺损伤引起的肠系膜淋巴细胞毒性发生在失血性休克后，可能是由于类花生酸代谢。在这个建议中，我们扩大了这种淋巴液的潜在生物活性，其毒性的必要条件，并解剖其成分。项目II对血液制品中积累的脂质和蛋白质进行了详细分析，重点是创伤的急性凝血病，目的是通过适当的血液复苏来尽量减少死亡率。项目本研究通过高渗溶液调节转录因子活化来研究减轻炎症的机制，并寻求应用吸入高渗盐水来减轻动物和人类的肺部炎症。为了验证这些想法，人类核心负责提供标本，收集数据，并更新创伤MOF数据库，同时严格遵守法规。一个充满活力的细胞，成像和蛋白质组学核心将为每个项目提供常用的人类细胞，设备和专业知识，以使用抗体以及先进的MS蛋白质组学进行先进的分子共定位和细胞计数。这些努力得到了经验丰富的行政核心的支持，旨在进一步提高我们三个机构（丹佛健康医疗中心，贝儿邦菲尔斯血液中心，科罗拉多大学健康科学中心）的实力，以公布创伤研究和改善病人护理。

DESCRIPTION (provided by applicant): Our global hypothesis is that two-way exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMED CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to (I) hemorrhagic shock, (II), transfusion (III), mechanisms of anti-inflammatory resuscitation. The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Project. I focuses on lung injury induced by the cytotoxic properties of mesenteric lymph that occur after hemorrhagic shock, presumably due to eicosanoid metabolism. In this proposal we expand on the potential bioactivity of this lymph, the condition necessary for its toxicity, and dissect its components. Project. II undertakes a detailed analysis of lipids and proteins accruing in blood products, focusing on the acute coagulopathy of trauma with the aim of minimizing mortality by proper blood resuscitation. Project. Ill examines mechanism of reducing inflammation by regulating transcription factor activation with hypertonic solution and seeks to apply inhaled hypertonic saline to reduce lung inflammation in animals and humans. To validate these ideas, the Human Core is charged with supplying specimens, gathering data, and updating the Trauma MOF database while remaining in strict regulatory compliance. A vigorous Cell, Imaging & Proteomics Core will provide each project with commonly used human cells, equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies as well and advanced MS proteomics . These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions (Denver Health Medical Center, Belle Bonfils Blood Center, University of Colorado Health Sciences Center) to promulgate Trauma Research and improve patient care.