Lung protein leakage in respiratory failure induced by a hybridoma making monoclonal antibody to the hydrophobic surfactant-associated polypeptide SP-B.
Adult mice were inoculated intraperitoneally with a hybridoma (8B5E) making monoclonal antibody to the porcine surfactant-associated polypeptide SP-B; this antibody cross-reacts with the corresponding polypeptide in the mouse surfactant system. Respiratory failure, developing 7-9 days after inoculation, was associated with a decrease in lung-thorax compliance determined during artificial ventilation, and an increase in the amount of protein including the specific antibody in lung lavage fluid. There was a statistically significant negative correlation between the compliance and the amount of protein as well as antibody recovered by lung lavage: r (log scale) = -0.69 and -0.82, respectively (P less than 0.01, both), but no decrease in the amount of phospholipids in lung lavage from animals inoculated with the hybridoma. Treatment with a large dose of porcine surfactant (about 320 mg phospholipids/kg body weight) had no positive effect on lung-thorax compliance during artificial ventilation; on the contrary, surfactant-treated animals showed a decrease in compliance similar to that seen in control animals after instillation of a similar volume of saline into the airways. We conclude that respiratory failure developing after inoculation with this hybridoma is probably at least in part mediated by flooding of the airspaces with antibody interfering with surfactant function.
Suzuki
Y
Y
Department of Molecular Pathology, Kyoto University, Japan.
Robertson
B
B
Fujita
Y
Y
Grossmann
G
G
Kogishi
K
K
Curstedt
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D008170:Lung Compliance / Q000502:physiology; D051379:Mice; D010743:Phospholipids / Q000032:analysis; D011510:Proteolipids / Q000276:immunology*; D011663:Pulmonary Surfactants / Q000276:immunology* / Q000627:therapeutic use; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants