Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice.
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 beta(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-alpha (TNF-alpha) 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-alpha 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.
Paine
R
R
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. rpaine@umich.edu
Morris
S B
SB
Jin
H
H
Wilcoxen
S E
SE
Phare
S M
SM
Moore
B B
BB
Coffey
M J
MJ
Toews
G B
GB
D000818:Animals; D018893:Bronchoalveolar Lavage; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000378:metabolism; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015289:Leukotrienes / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008863:Microspheres; D010587:Phagocytosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018821:CD18 Antigens; D018932:Chemokine CCL2; D015289:Leukotrienes; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor