Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1

J Exp Med. 2008 Nov 24;205(12):2711-6. doi: 10.1084/jem.20080759. Epub 2008 Oct 27.

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common beta chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR alpha chain, encoded in the X-chromosome pseudoautosomal region 1.

Publication types

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

MeSH terms

  • Animals
  • CD11b Antigen / metabolism
  • Child, Preschool
  • Chromosomes, Human, X / genetics*
  • Exons
  • Female
  • Genotype
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Male
  • Mice
  • Monocytes / cytology
  • Monocytes / metabolism
  • Pulmonary Alveolar Proteinosis / genetics*
  • Pulmonary Surfactants / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Signal Transduction / physiology
  • Turner Syndrome

Substances

  • CD11b Antigen
  • CSF2RA protein, human
  • Pulmonary Surfactants
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor