Surfactant metabolic consequences of overexpression of GM-CSF in the epithelium of GM-CSF-deficient mice.

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a regulator of surfactant metabolism because GM-CSF-deficient mice have abnormally slow clearance and catabolism of saturated phosphatidylcholine (Sat PC) and surfactant protein (SP)-A in airspaces and lung tissue. Overexpression of GM-CSF only in respiratory epithelial cells of mice deficient in GM-CSF using the SP-C promotor (GM-/-,SP-C-GM+/+) resulted in increased type II cell numbers and normalization of alveolar Sat PC pool sizes. Metabolic measurements demonstrated that incorporation of radiolabeled choline and palmitate was increased more than twofold, but the amount of radiolabeled Sat PC that accumulated in airspaces relative to the amount incorporated was decreased by 50% relative to normal GM+/+ mice. The clearance of dipalmitoylphosphatidylcholine and SP-B from the airspaces was more rapid for GM-/-,SP-C-GM+/+ mice than for GM+/+ mice. Loss of Sat PC and SP-B from the lungs (alveolar plus lung tissue) was similar in the two strains of mice. The normal surfactant pools in the GM-/-,SP-C-GM+/+ mice were achieved by the net effects of increases in type II cell numbers, increased incorporation, decreased accumulation, and increased reuptake rates for surfactant components, demonstrating the multiple effects of GM-CSF on surfactant metabolism.