GM-CSF regulates protein and lipid catabolism by alveolar macrophages

Metabolism of surfactant protein (SP) A and dipalmitoylphosphatidylcholine (DPPC) was assessed in alveolar macrophages isolated from granulocyte-macrophage colony-stimulated factor (GM-CSF) gene-targeted [GM(2/2)] mice, wild-type mice, and GM(2/2) mice expressing GM-CSF under control of the SP-C promoter element (SP-C-GM). Although binding and uptake of I-125-SP-A were significantly increased in alveolar macrophages from GM(2/2) compared with wild type or SP-C-GM mice, catabolism of I-125-SP-A was markedly decreased in GM(2/2) mice. Association of [H-3] DPPC with alveolar macrophages from GM(2/2), wild-type, and SP-C-GM mice was similar; however, catabolism of DPPC was markedly reduced in cells from GM(2/2) mice. Fluorescence-activated cell sorter analysis demonstrated decreased catabolism of rhodamine-labeled dipalmitoylphosphatidylethanolamine by alveolar macrophages from GM(2/2) mice. GM-CSF deficiency was associated with increased SP-A uptake by alveolar macrophages but with impaired surfactant lipid and SP-A degradation. These findings demonstrate the important role of GM-CSF in the regulation of alveolar macrophage lipid and SP-A catabolism.