Current Allergy and Asthma Reports

, Volume 10, Issue 5, pp 320–325 | Cite as

Immune Dysregulation in the Pathogenesis of Pulmonary Alveolar Proteinosis



Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the α chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense.


Pulmonary alveolar proteinosis PAP GM-CSF GM-CSF receptor Alveolar macrophages Surfactant homeostasis Immune deficiency Autoimmunity 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Margarita Martinez-Moczygemba
    • 1
  • David P. Huston
    • 1
  1. 1.Departments of Microbial and Molecular Pathogenesis and MedicineCollege of Medicine and Clinical Science and Translational Research Institute, Texas A&M Health Science CenterHoustonUSA

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