Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice

1 Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor 48109; and 2 Pulmonary Section, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48105 We hypothesized that pulmonary granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically involved in determining the functional capabilities of alveolar macrophages (AM) for host defense. To test this hypothesis, cells were collected by lung lavage from GM-CSF mutant mice [GM( / )] and C57BL/6 wild-type mice. GM( / ) mice yielded almost 4-fold more AM than wild-type mice. The percentage of cells positive for the 2 -integrins CD11a and CD11c was reduced significantly in GM( / ) AM compared with wild-type cells, whereas expression of CD11b was similar in the two groups. The phagocytic activity of GM( / ) AM for FITC-labeled microspheres was impaired significantly compared with that of wild-type AM both in vitro and in vivo (after intratracheal inoculation with FITC-labeled beads). Stimulated secretion of tumor necrosis factor- (TNF- ) and leukotrienes by AM from the GM( / ) mice was greatly reduced compared with wild-type AM, whereas secretion of monocyte chemoattractant protein-1 was increased. Transgenic expression of GM-CSF exclusively in the lungs of GM( / ) mice resulted in AM with normal or supranormal expression of CD11a and CD11c, phagocytic activity, and TNF- secretion. Thus, in the absence of GM-CSF, AM functional capabilities for host defense were significantly impaired but were restored by lung-specific expression of GM-CSF. lung; inflammation; growth factors; transgenic/knockout; granulocyte-macrophage colony-stimulating factor