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Research Article Free access | 10.1172/JCI119758

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

U Dirksen, R Nishinakamura, P Groneck, U Hattenhorst, L Nogee, R Murray, and S Burdach

Department of Pediatrics, Children's Hospital Medical Center, Heinrich Heine University, Düsseldorf, Germany.

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Department of Pediatrics, Children's Hospital Medical Center, Heinrich Heine University, Düsseldorf, Germany.

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Department of Pediatrics, Children's Hospital Medical Center, Heinrich Heine University, Düsseldorf, Germany.

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Department of Pediatrics, Children's Hospital Medical Center, Heinrich Heine University, Düsseldorf, Germany.

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Department of Pediatrics, Children's Hospital Medical Center, Heinrich Heine University, Düsseldorf, Germany.

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Department of Pediatrics, Children's Hospital Medical Center, Heinrich Heine University, Düsseldorf, Germany.

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Department of Pediatrics, Children's Hospital Medical Center, Heinrich Heine University, Düsseldorf, Germany.

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Published November 1, 1997 - More info

Published in Volume 100, Issue 9 on November 1, 1997
J Clin Invest. 1997;100(9):2211–2217. https://doi.org/10.1172/JCI119758.
© 1997 The American Society for Clinical Investigation
Published November 1, 1997 - Version history
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Abstract

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.

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