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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
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