Distinct changes in pulmonary surfactant homeostasis in common β-chain- and GM-CSF-deficient mice

Pulmonary alveolar proteinosis (PAP) is caused by inactivation of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM receptor common β-chain (βc) genes in mice [GM(−/−), βc(−/−)], demonstrating a critical role of GM-CSF signaling in surfactant homeostasis. To distinguish possible phenotypic differences in GM(−/−) and βc(−/−) mice, surfactant metabolism was compared in βc(−/−), GM(−/−), and wild-type mice. Although lung histology in βc(−/−) and GM(−/−) mice was indistinguishable, distinct differences were observed in surfactant phospholipid and surfactant protein concentrations and clearance from lungs of βc(−/−) and GM(−/−) mice. At 1–2 days of age, lung saturated phosphatidylcholine (Sat PC) pool sizes were higher in wild-type, βc(−/−), and GM(−/−) mice compared with wild-type adult mice. In wild-type mice, Sat PC pool sizes decreased to adult levels by 7 days of age; however, Sat PC increased with advancing age in βc(−/−) and GM(−/−) mice. Postnatal changes in Sat PC pool sizes were ...