GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D gene-targeted mice

Mice deficient in surfactant protein (SP) D develop increased surfactant po ol sizes and dramatic changes in alveolar macrophages and type II cells. To test the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates alveolar macrophage proliferation and activation and the type II cell hypertrophy seen in SP-D null mice, we bred SP-D and GM-CSF ge ne-targeted mice to obtain littermate double null, single null, and wild-ty pe mice. Bronchoalveolar lavage levels of phospholipid, protein, SP-D, SP-A , and GM-CSF were measured from 1 to 4 mo. There was an approximately addit ive accumulation of phospholipid, total protein, and SP-A at each time poin t. Microscopy showed normal macrophage number and morphology in GM-CSF null mice, numerous giant foamy macrophages and hypertrophic type II cells in S P-D null mice, and large but not foamy macrophages and mostly normal type I I cells in double null mice. These results suggest that the mechanisms unde rlying the alveolar surfactant accumulation in the SP-D-deficient and GM-CS F-deficient mice are different and that GM-CSF mediates some of the macroph age and type II cell changes seen in SP-D null mice.