Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation.
Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-deficient by homologous recombination maintain normal steady-state hematopoiesis but have an alveolar accumulation of surfactant lipids and protein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat PC) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls. Incorporation of radiolabeled palmitate and choline into Sat PC was higher in GM-CSF deficient mice than control mice, and no loss of labeled Sat PC occurred from the lungs of GM-CSF-deficient mice. Secretion of radiolabeled Sat PC to the alveolus was similar in GM-CSF-deficient and control mice. Labeled Sat PC and surfactant protein A (SP-A) given by tracheal instillation were cleared rapidly in control mice, but there was no measurable loss from the lungs of GM-CSF-deficient mice. The function of the surfactant from GM-CSF-deficient mice was normal when tested in preterm surfactant-deficient rabbits. GM-CSF deficiency results in a catabolic defect for Sat PC and SP-A.
Ikegami
M
M
Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, USA.
Ueda
T
T
Hull
W
W
Whitsett
J A
JA
Mulligan
R C
RC
Dranoff
G
G
Jobe
A H
AH
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008244:Lysophosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010168:Palmitates / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011817:Rabbits; D014132:Trachea
D008244:Lysophosphatidylcholines; D010168:Palmitates; D010713:Phosphatidylcholines; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002794:Choline