Trauma Primes Cells

创伤引发细胞

• 批准号: 8069421
• 负责人: ANIRBAN BANERJEE
• 金额: $ 44.97万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-30 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069421
• 关键词: Anti-Inflammatory Agents; Antibodies; Blood; CD14 Antigen; Cells; Charge; Clinical; Complex; Cytometry; Data; Databases; Drops; Endosomes; Endothelium; Equipment; Funding; Future; Heat shock proteins; Hemorrhagic Shock; Housing; Howard Temin Award; Human; Inflammation; Inflammatory; Injury; Institution; Lead; Lipids; Lung; Lymph; Mesentery; Molecular; Pathway interactions; Patients; Property; Proteins; Resuscitation; Sampling; Seasons; Signal Transduction; Specimen; Testing; Tissues; Toxic effect; Transfusion; Trauma; Trauma Research; cellular imaging; cytokine; cytotoxic; insight; novel; receptor; therapy development; trauma centers

This application is an extension of our funded 2000 Trauma Center application and a resubmission of our competing renewal thaw was awarded bridge funding for 2004-2005. Our global hypothesis is that twoway exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMES CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to hemorrhagic shock (I), transfusion (II), tissue injury (IV) and mechanisms of antiinflammatory resuscitation (V). The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Proj. I focuses on cytotoxic properties of mesenteric lymph that occur after hemorrhagic shock, presumably due to mesenteric hypoperfusion. In this proposal we expand on the potential bioactivity of this lymph, the condition necessary for its toxicity, and attempt to dissect its components. Proj. II undertakes a detailed analysis of analogous lipid metabolites accruing in lymph and stored blood, focusing on lung endothelium. Proj. Ill focused on heat shock proteins but is being dropped form this proposal. Proj. IV focuses on another type of ubiquitous intracellular protein HMGBP that may be the penultimate effector of inflammation, caused by either cytokines or LPS. Curiously, its signaling mechanism could lead to the same LPS receptor pathway. Proj. V challenges other projects that signaling by inflammatory agents depends on large signaling complexes that form as activated receptors are internalized. Therefore, by disrupting assembly of the endosome-scaffolded signaling modules, inflammatory manifestations might be avoided. To validate these ideas, the Human Core is charged with supplying specimens, gather data, and re-annotate the database while remaining in strict regulatory compliance. With young clinicians and bio-statisticians returning to query this powerful database, we reassess the impact of changing therapy and develop new hypotheses for bench-testing in future cycles. A vigorous Cell & Imaging Core will provide each project with commonly used human cells, and equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies. These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions to promulgate Trauma Research.

本申请是我们资助的2000年创伤中心申请的延伸，也是我们 竞争性的“复兴解冻”项目获得了2004-2005年的桥梁资金。我们的全球假设是， Human Core（容纳临床数据库和患者样本）与机械 对炎症信号的研究将帮助我们设计创伤原细胞的治疗方法。以来 在1993年的初始资金，我们的财政部数据库已经大大增长，产生新的见解，基本 出血性休克（I）、输血（II）、组织损伤（IV）和休克机制的固有问题 复苏（V）。这些项目仍然高度依赖彼此，并邀请人类 以进一步检验假设。项目。我的重点是肠系膜淋巴细胞毒性的性质，发生后， 失血性休克，可能是由于肠系膜灌注不足。在本提案中，我们扩展了 这种淋巴液的潜在生物活性，其毒性的必要条件，并试图解剖其 件.项目。II进行了详细的分析，类似的脂质代谢物积累在淋巴和 储存血液，关注肺内皮。项目Ill专注于热休克蛋白，但正在放弃 形成这个提案。项目IV关注另一种类型的普遍存在的细胞内蛋白HMGBP， 炎症的倒数第二效应物，由细胞因子或LPS引起。奇怪的是， 机制可能导致相同的LPS受体途径。项目。V挑战其他项目， 依赖于大的信号复合物，形成激活受体， 内化了因此，通过破坏内体支架化的信号模块的组装， 可以避免炎症表现。为了验证这些想法，人类核心负责 提供标本，收集数据，并重新注释数据库，同时保持严格的监管， 合规随着年轻的临床医生和生物统计学家返回查询这个强大的数据库，我们重新评估 改变治疗的影响，并为未来周期的实验室测试开发新的假设。一 细胞成像中心将为每个项目提供常用的人类细胞和设备， 利用抗体进行先进的分子共定位和细胞计数的专业知识。这些努力 由一个经验丰富的行政核心支持，旨在进一步增强我们三个机构的实力， 公布创伤研究