Damage to surfactant-specific protein in acute respiratory distress syndrome

Background Acute respiratory distress syndrome (ARDS) develops in associati on with many serious medical disorders. Mortality is at least 40%, and ther e is no specific therapy. A massive influx of activated neutrophils, which damage pulmonary vascular endothelium and alveolar epithelium, leads to alv eolar oedema and pulmonary surfactant dysfunction. In-vitro studies show th at neutrophil elastase can cleave surfactant-specific proteins and impair s urfactant function. If this happens in vivo in ARDS, the response to surfac tant therapy will be limited. Methods Samples of pulmonary surfactant were obtained from the lungs of 18 patients with ARDS and six healthy controls by bronchoalveolar lavage. We s eparated proteins in these samples according to molecular weight by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). We then use d western blotting with monoclonal antibody E8 to detect the major surfacta nt-specific protein A (SP-A). Findings By contrast with controls, 14 of 18 patients had evidence of in-vi vo damage to SP-A that resembled damage caused to SP-A when it is cleaved b y neutrophil elastase. Controls showed a single band of normal dimers at 66 kDa, whereas 14 of 18 patients showed multiple bands at 66 kDa, 55 kDA, an d 30-36 kDa, and six showed additional bands at 36-40 kDa. Interpretation Direct damage to surfactant-specific proteins occurs in lung s of patients with ARDS, probably by proteolysis. Trials of protein-contain ing therapeutic surfactant are in progress in ARDS, and our results indicat e that the frequent failure to maintain response may result from continuing damage to surfactant by products of activated neutrophils. A combination o f surfactant and antiprotease therapy may improve therapeutic prospects.