PATHOPHYSIOLOGY OF NEONATAL LUNG INJURY-INDUCED BY MONOCLONAL-ANTIBODY TO SURFACTANT PROTEIN-B

Near-term newborn rabbits were exposed via the airways to a monoclonal antibody to surfactant protein B and ventilated for 0-120 min. Contro l animals received nonspecific rabbit or mouse immunoglobulin G, salin e, or no material via the airways. Administration of the antibody at g reater than or equal to 40 mg/kg elicited an immediate, significant fa ll in lung-thorax compliance associated with progressive intra-alveola r edema and/or alveolar collapse and necrosis and desquamation of airw ay epithelium, and hyaline membranes. The vascular-to-alveolar leak of human albumin and human immunoglobulin G, injected intravenously at b irth and determined in lung lavage fluid 60-120 min after instillation of the antibody, was 1.8% for the left lung, with no difference betwe en the markers. The average leak in control animals ventilated for 120 min was <0.3% (P < 0.05). Cytospin preparations of lung lavage fluid from animals exposed to the antibody showed significantly increased re cruitment of neutrophilic granulocytes. The pathology and pathophysiol ogy of neonatal lung injury induced by the monoclonal antibody to surf actant protein B probably reflect a combination of direct inactivation of surfactant and an inflammatory response triggered by the immune re action.