Immune dysregulation in the pathogenesis of pulmonary alveolar proteinosis

Margarita Martinez-Moczygemba, David P. Huston

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)320-325
Number of pages6
JournalCurrent Allergy and Asthma Reports
Volume10
Issue number5
DOIs
StatePublished - Sep 2010

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Immune dysregulation in the pathogenesis of pulmonary alveolar proteinosis'. Together they form a unique fingerprint.

Cite this