GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis

Am J Respir Crit Care Med. 1997 Dec;156(6):1999-2002. doi: 10.1164/ajrccm.156.6.9612119.


Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an excessive accumulation of surfactant lipids and proteins in the alveolar space. In mice with a homozygous deletion of granulocyte macrophage-colony stimulating factor (GM-CSF), their phenotype mimics PAP. To evaluate whether the knockout mouse model mimics human disease, we evaluated GM-CSF expression in alveolar macrophages from a patient with PAP. We performed multiple whole lung lavages on a patient with PAP, and cultured BAL cells in the presence or absence of LPS. In contrast to the GM-CSF knockout mouse, human BAL cells from a patient with PAP expressed mRNA for GM-CSF following LPS stimulation. However, similar to the knockout mouse, GM-CSF protein release from BAL cells was undetectable with or without LPS. BAL cells from normal human controls released GM-CSF in abundance after LPS stimulation. In BAL cells from the patient with PAP, neutralization of interleukin-10 (IL-10) by anti-IL-10 antibody, resulted in enhanced GM-CSF production. Thus, alveolar macrophages from a PAP lung have deficient GM-CSF production analogous to the GM-CSF knockout mice; in contrast, human cells from a PAP lung have an intact GM-CSF gene. This case report illustrates an important difference between the knockout mouse model of PAP and the human disease.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / cytology
  • Cells, Cultured
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-10 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Macrophages, Alveolar / metabolism
  • Pulmonary Alveolar Proteinosis / genetics*
  • Pulmonary Alveolar Proteinosis / metabolism
  • RNA, Messenger / analysis


  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor