LUNG MACROPHAGE MODULATION OF PULMONARY EDEMA

成人呼吸窘迫综合征（ARDS），一种非心源性或 渗透性肺水肿，是死亡的主要原因， 住院病人。 该综合征的发病机制与 急性弥漫性肺微血管损伤，发生在 诱发性临床疾病（如细菌性败血症）的发作。 目前的研究表明，多形核中性粒细胞在 在产生肺血管病变中起关键作用， 综合征 炎症过程中发生的一系列事件 其产生中性粒细胞活化和随后的肺泡毛细血管 膜损伤仍不清楚。 假设血管内 补体激活介导的中性粒细胞激活尚未获得 普遍接受。 最近的研究已经将注意力转移到肺部， 一种能够促进血管内 效应细胞激活。 该提案将利用支气管肺泡 灌洗作为从肺获得免疫效应细胞的方法， 研究随着综合症发展的炎症过程。 因为 从我们的试点研究的初步数据，在这一建议的重点将是 以及它在吸引 中性粒细胞进入空气空间，随后放大它们的活性， 产生伤害。 通过研究处于不同发展阶段的患者， 我们的目标是：1）评估巨噬细胞的状态 2）通过测量代谢和杀细胞活性来评估“活化”， 肺泡巨噬细胞是否分泌炎性物质， 中性粒细胞活性，3）表征 炎症物质分泌的风险和ARDS巨噬细胞在体外。 这项研究的结果将使人们更好地了解 细胞调节肺部炎症反应。 它将 提供了有关中性粒细胞流入气道的新信息， 该事件与微血管损伤的关系。

The adult respiratory distress syndrome (ARDS), a non-cardiac or permeability pulmonary edema, is a major cause of mortality among hospitalized patients. The pathogenesis of the syndrome is linked to acute, diffuse pulmonary microvascular injury which occurs following the onset of predisposing clinical conditions (eg, bacterial septicemia). Current research indicates that the polymorphonuclear neutrophil plays a critical role in producing the pulmonary vascular lesions which lead to the syndrome. The sequence of events occurring in the inflammatory process which produces neutrophil activation and subsequent alveolar-capillary membrane injury remain unclear. The hypothesis that intravascular complement activation mediates neutrophil activation has not gained universal acceptance. Recent studies have shifted attention to the lung as a source of cell-derived substances capable of promoting intravascular effector cell activation. This proposal will utilize bronchoalveolar lavage as a method of obtaining immune effector cells from the lung to study the inflammatory process as the syndrome develops. Because of preliminary data from our pilot studies, emphasis in this proposal will be placed on the alveolar macrophage and its potential role in attracting neutrophils to the airspace and subsequently amplifying their activity to produce injury. By studying patients at various stages of development of the syndrome our aims will be to: 1) assess the state of macrophage "activation" by measuring metabolic and cytocidal activity, 2) assess whether alveolar macrophages secrete phlogistic substances which modulate neutrophil activity, 3) characterize the lipid and peptide nature of phlogistic substances secreted by at-risk and ARDS macrophages in-vitro. The results of this research will lead to a greater understanding of cellular modulation of the inflammatory response in the lung. It will provide new information concerning neutrophil influx into the airways and the relationship of this event to microvascular injury.