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 pool 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 gene-targeted mice to obtain littermate double null, single null, and wild-type 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 additive accumulation of phospholipid, total protein, and SP-A at each time point. Microscopy showed normal macrophage number and morphology in GM-CSF null mice, numerous giant foamy macrophages and hypertrophic type II cells in SP-D null mice, and large but not foamy macrophages and mostly normal type II cells in double null mice. These results suggest that the mechanisms underlying the alveolar surfactant accumulation in the SP-D-deficient and GM-CSF-deficient mice are different and that GM-CSF mediates some of the macrophage and type II cell changes seen in SP-D null mice.
Hawgood
S
S
Department of Pediatrics, Cardiovascular Research Institute, University of California, San Francisco, CA 94118-1245, USA. hawgood@itsa.ucsf.edu
Akiyama
J
J
Brown
C
C
Allen
L
L
Li
G
G
Poulain
F R
FR
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003433:Crosses, Genetic; D018390:Gene Targeting; D005838:Genotype; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D006579:Heterozygote; D006720:Homozygote; D008168:Lung / Q000166:cytology / Q000648:ultrastructure; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015388:Organelles / Q000648:ultrastructure; D010641:Phenotype; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D006023:Glycoproteins; D010743:Phospholipids; D011506:Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor