Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression

J Clin Invest. 1997 Nov 1;100(9):2211-7. doi: 10.1172/JCI119758.


Pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder of genetic or acquired etiologies. In some cases congenital PAP is associated with hereditary surfactant protein (SP)-B deficiency. To date, the molecular defect in the majority of patients with PAP has not been identified. In mice, PAP has been generated by targeted deletion of the genes for either the GM-CSF/IL-3/IL-5 receptor common beta chain (beta c) or GM-CSF. Here, we describe an expression defect of beta c in three of seven pediatric patients with PAP and in one patient with severe lung disease suspected to be PAP. The patients failed to express normal levels of beta c as shown by flow cytometry. Strikingly reduced or absent function of beta c was demonstrated by ligand binding studies and progenitor clonogenic assays. Analysis of beta c DNA revealed a point mutation from proline to threonine at codon 602 in one patient. Our findings provide evidence that a defect in the expression of a hematopoietic cytokine receptor is associated with human PAP.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Child, Preschool
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Hematopoiesis
  • Humans
  • Infant
  • Kinetics
  • Point Mutation
  • Proteolipids / metabolism
  • Pulmonary Alveolar Proteinosis / metabolism*
  • Pulmonary Surfactants / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / deficiency*
  • Receptors, Interleukin / deficiency*
  • Receptors, Interleukin-3 / deficiency*
  • Receptors, Interleukin-5


  • Proteolipids
  • Pulmonary Surfactants
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptors, Interleukin
  • Receptors, Interleukin-3
  • Receptors, Interleukin-5
  • Granulocyte-Macrophage Colony-Stimulating Factor