Antibody to Surfactant Protein A Increases Sensitivity of Pulmonary Surfactant to Inactivation by Fibrinogen in vivo

摘要

It has been suggested that surfactant protein-A (SP-A) protects surfactant activity from inhibitors such as fibrinogen. Substantial evidence indicates that, inhibition of surfactant activity is often important in the pathogenesis of acute respiratory failure. Studies on surfactant function in the pulsating bubble surfactometer imply that SP-A helps to maintain low surface tension in the presence of inhibitors such as fibrinogen. We tested whether SP-A acts in this way in vivo. Rabbit pups, 29 d gestational age, were treated with a monoclonal antibody to rabbit SP-A (R5) followed by fibrinogen, or with control preparations (normal IgC and saline, respectively). Lung compliance was measured during ventilation throughout these experiments. Air-space volume and pulmonary edema were quantitated morphometrically. Animals receiving anti-SP-A antibody + fibrinogen showed substantial and significant impairment in lung compliance compared with control littermates receiving normal IgC and/or saline. Lungs from these animals showed decreased pulmonary air-space volume and increased alveolar edema. We conclude that SP-A protects pulmonary surfactant from inhibition by fibrinogen in vivo. This protective activity may be important in the pathogenesis of both adult and neonatal respiratory distress syndromes, and it may also be useful in devising therapies for these diseases.