Pulmonary alveolar proteinosis is a disease of decreased availability of GM-CSF rather than an intrinsic cellular defect

Clin Immunol. 2000 May;95(2):85-92. doi: 10.1006/clim.2000.4859.


Granulocyte-macrophage colony stimulating factor (GM-CSF) deficient mice develop a pulmonary alveolar proteinosis (PAP) syndrome which is corrected by the administration/expression of GM-CSF. These observations implicate GM-CSF in the pathogenesis of human PAP. We hypothesized that human PAP may involve an intrinsic cellular defect in monocytes/macrophages with an inability to produce GM-CSF and/or respond to GM-CSF. Thus, we investigated the cytokine responses to GM-CSF and LPS from peripheral blood monocytes and alveolar macrophages from patients with idiopathic PAP and healthy controls. Macrophage inflammatory protein-1-alpha (MIP) was measured from GM-CSF-stimulated cells and GM-CSF was measured from LPS-stimulated cells by ELISA. The MIP and GM-CSF production by monocytes and alveolar macrophages did not differ between PAP patients and healthy controls. Growth of the GM-CSF-dependent human myeloid cell line TF-1 was inhibited by serum from all patients studied (n = 10) and all patients had anti-GM-CSF antibody in their serum. The BAL from PAP patients had less detectable GM-CSF by ELISA than healthy controls (P = 0.05); in contrast, the inhibitory cytokine, interleukin-10 (IL-10), was increased in PAP compared to controls (P = 0.04). IL-10 is a potent inhibitor of LPS-stimulated GM-CSF production from healthy control alveolar macrophages. These studies are the first to demonstrate that circulating monocytes and alveolar macrophages from PAP patients are able to synthesize GM-CSF and respond to GM-CSF, suggesting no intrinsic abnormalities in GM-CSF signaling. In addition, these observations suggest that PAP in a subset of patients is the result of decreased availability of GM-CSF due to GM-CSF blocking activity and reduced GM-CSF production by IL-10.

Publication types

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

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / chemistry
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Lung / metabolism
  • Macrophages, Alveolar / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Pulmonary Alveolar Proteinosis / pathology*


  • Granulocyte-Macrophage Colony-Stimulating Factor