Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor which neutralizes granulocyte-macrophage colony stimulating factor

N Tanaka; J Watanabe; T Kitamura; Y Yamada; S Kanegasaki; K Nakata

doi:10.1016/s0014-5793(98)01668-8

Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor which neutralizes granulocyte-macrophage colony stimulating factor

FEBS Lett. 1999 Jan 15;442(2-3):246-50. doi: 10.1016/s0014-5793(98)01668-8.

Authors

N Tanaka¹, J Watanabe, T Kitamura, Y Yamada, S Kanegasaki, K Nakata

Affiliation

¹ Laboratory of Culture Collection, The Institute of Medical Science, The University of Tokyo, Japan.

PMID: 9929010
DOI: 10.1016/s0014-5793(98)01668-8

Abstract

Mice deficient in granulocyte-macrophage colony stimulating factor (GM-CSF) develop pulmonary alveolar proteinosis (PAP). We found that bronchoalveolar lavage fluid (BALF) from 11 patients with idiopathic pulmonary alveolar proteinosis (IPAP) suppressed the growth of peripheral blood monocytes and TF-1 cells, a cell line dependent on either GM-CSF or interleukin-3 (IL-3). The inhibitory effect of PAP-BALF occurred only when TF-1 cells were cultured with GM-CSF but not when cultured with IL-3, suggesting that PAP-BALF contains a factor that specifically interferes with GM-CSF function. 125I-GM-CSF binding to TF-1 cells was prevented in the presence of BALF from IPAP patients. Furthermore, cross-linking of 125I-GM-CSF to IPAP-BALF produced two major bands on SDS-PAGE; these bands were not observed in normal BALF. These data suggest that IPAP is caused by expression of binding factor(s) which inhibit GM-CSF function in the lung.

MeSH terms

Binding, Competitive
Biological Factors / analysis
Biological Factors / metabolism
Biological Factors / pharmacology*
Bronchoalveolar Lavage Fluid / chemistry*
Cell Division / drug effects
Cell Line
Cell Survival / drug effects
Cells, Cultured
Cross-Linking Reagents
Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Humans
Interleukin-3 / pharmacology
Lung / chemistry
Lung / metabolism*
Molecular Weight
Monocytes
Protein Binding
Pulmonary Alveolar Proteinosis / etiology
Pulmonary Alveolar Proteinosis / metabolism*
Pulmonary Alveolar Proteinosis / pathology
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism

Substances

Biological Factors
Cross-Linking Reagents
Interleukin-3
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor