BACTERIAL MODULATION OF LUNG INFLAMMATORY RESPONSE

肺部炎症反应的细菌调节

• 批准号: 6638845
• 负责人: THOMAS A RUSSO
• 金额: $ 35.33万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6638845
• 关键词: Escherichia coli; RNase protection assay; bacterial capsules; bacterial pneumonia; bacterial polysaccharides; bacterial somatic antigen; bactericidal immunity; bioassay; cell migration; chemotaxis; cytokine; enzyme linked immunosorbent assay; gram negative bacteria; host organism interaction; immunocytochemistry; immunoregulation; inflammation; laboratory rat; lipopolysaccharides; lung injury; macrophage inflammatory proteins; neutrophil; pathologic process; respiratory infections

DESCRIPTION (Unedited Applicant's Abstract): Gram-negative bacilli (GNB) are pathogens that are capable of causing severe, life-threatening pneumonia. More than 60 percent of nosocomial pneumonias are caused by GNB and associated mortality rates are often >50 percent. Over the last 10-15 years, there has been little improvement in outcome from this infection. As a result, this syndrome continues to cause significant morbidity and mortality and strongly contributes to the economic burden of our national health care system. The successful use of immune intervention in the treatment or modulation of infections has marked the beginning of a new era in the management of infectious diseases. There exists a delicate balance between an efficacious and injurious host defense response. An understanding of the host response in GNB pneumonia and how bacterial components affect this response will, in turn, lead to the development of rapid diagnostic tests that will enable the clinician to effectively utilize a variety of biologic modulators. It is also necessary to understand the relative role of bacterial components versus host factors in mediating damage to the lungs prior to therapeutic manipulations on which little is known. This information will enable us to appreciate the relative risk benefit ratio of altering the host response. Further, a more precise clarification of which host components are damaged is also needed. This knowledge may identify independent therapeutic interventions. Their global hypothesis is that surface components of GNB and/or secreted proteins differentially alter host antibacterial defenses and directly, and/or indirectly (by inflammatory mechanisms) promote lung injury. Preliminary data supports this hypothesis. These responses will have significant implications when attempting therapeutic immune interventions. The goals of this proposal are to determine the mechanisms by which the bacterial capsule and 0-specific antigen modulate neutrophil recruitment into the lungs in a diametrical manner and extend our evaluations on the relative roles of bacterial factors (e.g. hemolysin) and bacterially induced host response elements in directly mediating the pathogenesis of lung injury.

描述（未经编辑的申请人的摘要）：革兰氏阴性杆菌（GNB）是 能够引起严重，威胁生命的肺炎的病原体。更多的 超过60％的医院肺炎是由GNB引起的，相关的 死亡率通常> 50％。在过去的10 - 15年中， 这种感染的结果几乎没有改善。结果，这个 综合征继续引起明显的发病率和死亡率，并且强烈 为我们的国家医疗保健系统的经济负担做出了贡献。 成功地在治疗或调节中成功使用免疫干预 感染标志着新时代的开始 传染病。有效和 有害的东道国国防反应。对GNB中宿主反应的理解 肺炎和细菌成分如何影响这种反应将依次铅 开发快速诊断测试，这将使临床医生能够 有效地利用各种生物调节剂。也有必要 了解细菌成分与宿主因子的相对作用 在治疗操作之前，对肺部的损害进行介导 鲜为人知。这些信息将使我们能够欣赏亲戚 改变宿主响应的风险益处比率。此外，更精确 还需要澄清哪些主机组件受损。这 知识可以识别独立的治疗干预措施。 他们的全球假设是GNB和/或分泌的表面成分 蛋白质差异改变宿主抗菌防御，直接和/或 间接（通过炎症机制）促进肺损伤。初步数据 支持这一假设。这些回应将具有重大影响 尝试治疗性免疫干预时。该提议的目标 确定细菌胶囊和0特异性的机制 抗原以直径的方式调节嗜中性粒细胞募集到肺部 并扩展我们对细菌因子相对作用的评估（例如 血素蛋白）和细菌诱导的宿主反应元件直接介导 肺损伤的发病机理。