Exogenous porcine surfactant (Curosurf) is inactivated by monoclonal antibody to the surfactant-associated hydrophobic protein SP-B.
A monoclonal antibody to the surfactant-associated hydrophobic protein SP-B was added at various concentrations to a standard preparation of porcine surfactant (Curosurf 10 mg/ml), and surface properties were evaluated with pulsating bubble. Retarded adsorption of surfactant was observed at antibody concentrations > or = 0.5 mg/ml and significantly increased values for minimum surface tension were observed at antibody concentrations > or = 1 mg/ml. In vivo effects of the antibody were tested in immature newborn rabbits ventilated with a standardized sequence of insufflation pressures. Animals receiving 0.1 ml surfactant (80 mg/ml) mixed with antibody at concentrations > or = 4 mg/ml had low tidal volumes, poor lung stability in pressure-volume recordings, poor alveolar expansion in histological sections and widespread epithelial necrosis in peripheral airways. Admixtures of IgG had no such effects. We conclude that this monoclonal antibody inactivates exogenous porcine surfactant, probably by preventing fast adsorption of surfactant lipids to the alveolar air-liquid interfaces.
Kobayashi
T
T
Department of Anesthesiology, School of Medicine, Kanazawa University, Japan.
Robertson
B
B
Grossmann
G
G
Nitta
K
K
Curstedt
T
T
Suzuki
Y
Y
D000327:Adsorption; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001688:Biological Products; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D010743:Phospholipids; D011510:Proteolipids / Q000276:immunology*; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000276:immunology*; D011817:Rabbits; D013500:Surface Tension; D013990:Tidal Volume
D000911:Antibodies, Monoclonal; D001688:Biological Products; D004338:Drug Combinations; D007074:Immunoglobulin G; D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants; C068291:poractant alfa