Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages

Curr Opin Immunol. 2009 Oct;21(5):514-21. doi: 10.1016/j.coi.2009.09.004. Epub 2009 Sep 30.


Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of pulmonary surfactant, respiratory insufficiency, and increased infections. It occurs in various clinical settings that disrupt surfactant catabolism in alveolar macrophages, including a relatively more common autoimmune disease caused by GM-CSF autoantibodies and a rare congenital disease caused by CSF2RA mutations. Recent results demonstrate that GM-CSF is crucial for alveolar macrophage terminal differentiation and immune functions, pulmonary surfactant homeostasis, and lung host defense. GM-CSF is also required to determine the basal functional capacity of circulating neutrophils, including adhesion, phagocytosis, and microbial killing. PAP research has illuminated the crucial role of GM-CSF in innate immunity and led to novel therapy for PAP and the potential use of anti-GM-CSF therapy in other common disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology
  • Models, Biological
  • Protein Binding
  • Pulmonary Alveolar Proteinosis / immunology*
  • Pulmonary Alveolar Proteinosis / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism


  • CSF2RA protein, human
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor