SURFACTANT METABOLISM IN TRANSGENIC MICE AFTER GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR ABLATION

Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-de ficient by homologous recombination maintain normal steady-state hemat opoiesis but have an alveolar accumulation of surfactant lipids and pr otein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat P C) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls. Incorporation of radiolabeled palmitate an d choline into Sat PC was higher in GM-CSF deficient mice than control mice, and no loss of labeled Sat PC occurred from the lungs of GM-CSF -deficient mice. Secretion of radiolabeled Sat PC to the alveolus was similar in GM-CSF-deficient and control mice. Labeled Sat PC and surfa ctant protein A (SP-A) given by tracheal instillation were cleared rap idly in control mice, but there was no measurable loss from the lungs of GM-CSF-deficient mice. The function of the surfactant from GM-CSF-d eficient mice was normal when tested in preterm surfactant-deficient r abbits. GM-CSF deficiency results in a catabolic defect for Sat PC and SP-A.