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.
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