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

TitlePulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1.
Publication TypeJournal Article
Year of Publication2008
AuthorsMartinez-Moczygemba, M, Doan, ML, Elidemir, O, Fan, LL, Cheung, SWai, Lei, JT, Moore, JP, Tavana, G, Lewis, LR, Zhu, Y, Muzny, DM, Gibbs, RA, Huston, DP
JournalJ Exp Med
Volume205
Issue12
Pagination2711-6
Date Published2008 Nov 24
ISSN1540-9538
KeywordsAnimals, CD11b Antigen, Child, Preschool, Chromosomes, Human, X, Exons, Female, Genotype, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Male, Mice, Monocytes, Pulmonary Alveolar Proteinosis, Pulmonary Surfactants, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Signal Transduction, Turner Syndrome
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.

DOI10.1084/jem.20080759
Alternate JournalJ. Exp. Med.
PubMed ID18955567
PubMed Central IDPMC2585851
Grant ListU19 AI071130 / AI / NIAID NIH HHS / United States
R01 AI063178 / AI / NIAID NIH HHS / United States
AI36936 / AI / NIAID NIH HHS / United States
AI063178 / AI / NIAID NIH HHS / United States
AI071130 / AI / NIAID NIH HHS / United States
R01 AI036936 / AI / NIAID NIH HHS / United States