Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation

Am J Physiol. 1996 Apr;270(4 Pt 1):L650-8. doi: 10.1152/ajplung.1996.270.4.L650.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine / analogs & derivatives
  • 1,2-Dipalmitoylphosphatidylcholine / metabolism
  • Animals
  • Choline / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Lysophosphatidylcholines / administration & dosage
  • Lysophosphatidylcholines / pharmacokinetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Palmitates / metabolism
  • Phosphatidylcholines / metabolism
  • Proteolipids / metabolism*
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants / metabolism*
  • Rabbits
  • Trachea


  • Lysophosphatidylcholines
  • Palmitates
  • Phosphatidylcholines
  • Proteolipids
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants
  • 1,2-Dipalmitoylphosphatidylcholine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Choline