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.

该申请是我们资助的 2000 创伤中心申请的延伸，也是我们的重新提交 竞争更新解冻获得了2004-2005年过桥资金。我们的全球假设是双向的 人类核心（容纳临床数据库和患者样本）与机械之间的交换 对炎症信号传导的研究将帮助我们设计针对创伤引发细胞的疗法。自从 自 1993 年获得初始资金以来，我们的 MOF 数据库已大幅增长，对基本原理产生了新颖的见解 失血性休克（I）、输血（II）、组织损伤（IV）固有的问题和抗炎机制 复苏（五）。这些项目仍然高度依赖彼此，并邀请人类 进一步检验假设的核心。项目。我重点关注肠系膜淋巴的细胞毒性特性，这些特性发生在 失血性休克，可能是由于肠系膜灌注不足所致。在本提案中，我们扩展了 该淋巴液的潜在生物活性，其毒性所必需的条件，并尝试解剖其 成分。项目。 II 对淋巴和淋巴中产生的类似脂质代谢物进行了详细分析 储存血液，集中于肺内皮。项目。我专注于热休克蛋白，但正在被放弃 形成本提案。项目。 IV 重点关注另一种普遍存在的细胞内蛋白 HMGBP，它可能是 由细胞因子或脂多糖引起的炎症的倒数第二效应器。奇怪的是，它的信号 机制可能导致相同的 LPS 受体途径。项目。 V 挑战其他项目，表明 炎症因子的作用取决于激活受体形成的大型信号复合物 内化了。因此，通过破坏内体支架信号模块的组装， 炎症表现可能是可以避免的。为了验证这些想法，人类核心负责 提供样本、收集数据并重新注释数据库，同时保持严格的监管 遵守。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 改变疗法的影响并为未来周期的台架测试制定新的假设。一个 活力细胞与影像核心将为每个项目提供常用的人体细胞、设备和 使用抗体进行高级分子共定位和细胞计数的专业知识。这些努力是 得到经验丰富的行政核心的支持，该核心旨在进一步提高我们三个机构的实力 颁布创伤研究。