Granulocyte macrophage-colony-stimulating factor mRNA is stabilized in airway eosinophils and peripheral blood eosinophils activated by TNF-alpha plus fibronectin

Airway eosinophils show prolonged in vitro survival compared with peripheral blood eosinophils (PBEos). Recent studies have shown that autocrine production and release of GM-CSF is responsible for enhanced survival, but the mechanisms controlling cytokine production remain obscure. We compared GM-CS...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-04, Vol.166 (7), p.4658-4663
Main Authors: Esnault, S, Malter, J S
Format: Article
Language:English
Subjects:
Bronchi - cytology
Bronchi - immunology
Bronchi - metabolism
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - cytology
Cell Movement - immunology
Cell Survival - drug effects
Cell Survival - immunology
Cells, Cultured
Drug Combinations
Eosinophils - drug effects
Eosinophils - immunology
Eosinophils - metabolism
Fibronectins - pharmacology
Granulocyte-Macrophage Colony-Stimulating Factor - blood
Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Humans
RNA, Messenger - blood
RNA, Messenger - metabolism
Tumor Necrosis Factor-alpha - pharmacology
Up-Regulation - immunology
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Summary:Airway eosinophils show prolonged in vitro survival compared with peripheral blood eosinophils (PBEos). Recent studies have shown that autocrine production and release of GM-CSF is responsible for enhanced survival, but the mechanisms controlling cytokine production remain obscure. We compared GM-CSF mRNA decay in eosinophils from bronchoalveolar lavage (BALEos) after allergen challenge or from PBEos. BALEos showed prolonged survival in vitro (60% at 4 days) and expressed GM-CSF mRNA. The enhanced survival of BALEos was 75% inhibited at 6 days by neutralizing anti-GM-CSF Ab. Based on transfection studies, GM-CSF mRNA was 2.5 times more stable in BALEos than in control PBEos. Treatment of PBEos with fibronectin and TNF-alpha increased their in vitro survival, GM-CSF mRNA expression, and GM-CSF mRNA stability to a comparable level as seen in BALEos. These data suggest that TNF-alpha plus fibronectin may increase eosinophil survival in vivo by controlling GM-CSF production at a posttranscriptional level.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.166.7.4658