The proposed investigations emphasize attempts to prevent or ameliorate acute lung injury (ALI). Surfactant may be critically important in maintaining lung function and minimizing an acute inflammatory response to various insults. Surfactant supplementation may protect against ALI related to hyperoxic exposure, ventilator-induced lung injury, or reperfusion lung injury. Products of activated neutrophils are likely to contribute to ALI. Since surfactant phospholipids have been shown to significantly decrease neutrophil respiratory burst oxidase (RBO) activity and superoxide anion production. This project proposes to explore further both the interaction(s) between lung surfactant and airway phagocytes and also the benefits that may occur by enhancing airway surfactant pools in animals subjects to stresses that are known both to perturb the lung surfactant system and to induce ALI.
The specific aims are to: (1) define the mechanisms whereby surfactant components modulate phagocyte function, with emphasis on NADPH- dependent respiratory burst oxidase activity. (2) characterize the effects of in vitro and in vivo transgene expression on the surfactant system, and test the hypothesis that augmentation of endogenous phospholipid pools provides protection against several forms of acute lung injury; and (3) measure BAL pro-inflammatory cytokine level in samples from ARDS patients, and determine by indirect means (measurement of oxidized alpha1- proteinase inhibitor, alpha1-PI) if oxidant production is diminished in patients receiving surfactant. In addition, surfactant ability to modulate phagocyte function will be assessed.
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