BACTERIAL MODULATION OF LUNG INFLAMMATORY RESPONSE

描述(未经编辑的申请人摘要)：革兰氏阴性杆菌(GNB)为 能够引起严重的、危及生命的肺炎的病原体。更多 超过60%的院内肺炎是由GNB和与之相关的 死亡率通常为50%。在过去的10-15年里，有 这次感染的结果几乎没有改善。因此，这一点 综合症继续导致显著的发病率和死亡率，并强烈 增加了我们国家医疗保健系统的经济负担。 免疫干预在治疗或调节慢性粒细胞白血病中的成功应用 感染标志着管理的新纪元的开始 传染病。在有效和有效之间存在微妙的平衡 伤害性宿主防御反应。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反过来导致 开发快速诊断测试，使临床医生能够 有效利用多种生物调节剂。还有必要 了解细菌成分与宿主因素的相对作用 在对其进行治疗之前调解对肺的损害 人们对此知之甚少。这些信息将使我们能够欣赏到 改变宿主反应的风险收益比率。更进一步，一个更精确的 还需要澄清哪些主机组件受损。这 知识可以确定独立的治疗干预措施。 他们的全球假说是GNB和/或分泌物的表面成分 蛋白质以不同方式改变宿主的抗菌防御系统，并直接，和/或 间接地(通过炎症机制)促进肺损伤。初步数据 支持这一假设。这些回应将产生重大影响 当尝试治疗性免疫干预时。这项提案的目标是 是为了确定细菌胶囊和0-特异性的机制 抗原以一种相反的方式调节中性粒细胞重新进入肺内 并扩大我们对细菌因素相对作用的评估(例如 溶血素)和细菌诱导的宿主反应元件直接介导 肺损伤的发病机制。

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.