Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor which neutralizes granulocyte-macrophage colony stimulating factor

FEBS Lett. 1999 Jan 15;442(2-3):246-50. doi: 10.1016/s0014-5793(98)01668-8.


Mice deficient in granulocyte-macrophage colony stimulating factor (GM-CSF) develop pulmonary alveolar proteinosis (PAP). We found that bronchoalveolar lavage fluid (BALF) from 11 patients with idiopathic pulmonary alveolar proteinosis (IPAP) suppressed the growth of peripheral blood monocytes and TF-1 cells, a cell line dependent on either GM-CSF or interleukin-3 (IL-3). The inhibitory effect of PAP-BALF occurred only when TF-1 cells were cultured with GM-CSF but not when cultured with IL-3, suggesting that PAP-BALF contains a factor that specifically interferes with GM-CSF function. 125I-GM-CSF binding to TF-1 cells was prevented in the presence of BALF from IPAP patients. Furthermore, cross-linking of 125I-GM-CSF to IPAP-BALF produced two major bands on SDS-PAGE; these bands were not observed in normal BALF. These data suggest that IPAP is caused by expression of binding factor(s) which inhibit GM-CSF function in the lung.

MeSH terms

  • Binding, Competitive
  • Biological Factors / analysis
  • Biological Factors / metabolism
  • Biological Factors / pharmacology*
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Cell Division / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cross-Linking Reagents
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Interleukin-3 / pharmacology
  • Lung / chemistry
  • Lung / metabolism*
  • Molecular Weight
  • Monocytes
  • Protein Binding
  • Pulmonary Alveolar Proteinosis / etiology
  • Pulmonary Alveolar Proteinosis / metabolism*
  • Pulmonary Alveolar Proteinosis / pathology
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism


  • Biological Factors
  • Cross-Linking Reagents
  • Interleukin-3
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor