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Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro

S Zhang, Q Mohammed, A Burbidge, CM Morland, WR Roche
European Respiratory Journal 1996 9: 1839-1846; DOI:
S Zhang
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Q Mohammed
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A Burbidge
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CM Morland
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WR Roche
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Abstract

Mechanisms of eosinophil accumulation and activation in the bronchial mucosa are crucial for the pathogenesis of asthma. The location of specialized fibroblasts, myofibroblasts, beneath the bronchial basement membrane and their proximity to infiltrating eosinophils potentially enable the myofibroblasts to modulate eosinophil survival and function in asthma. The aim of this study was to investigate the effects of bronchial myofibroblasts on eosinophil survival in vitro. Eosinophils from human peripheral blood were exposed to cell cultures from bronchial myofibroblasts and to myofibroblast-conditioned media. Eosinophil viability was assessed and granulocyte/macrophage colony-stimulating factor (GM-CSF) production was examined in co-culture supernatants and as messenger ribonucleic acid (mRNA) in myofibroblasts. Eosinophil survival was significantly increased and eosinophil apoptosis was inhibited by co-culture with myofibroblasts. Conditioned medium from tumour necrosis factor-alpha (TNF-alpha)-stimulated myofibroblasts also prolonged eosinophil survival. This effect could be blocked by GM-CSF antibody. GM-CSF mRNA and secretion from myofibroblasts were increased in co-cultures and by eosinophil-conditioned medium. Addition of antibodies to TNF-alpha and interleukin-1 alpha (IL-1 alpha) to co-cultures resulted in significant reduction both in eosinophil survival and GM-CSF levels. Blocking of fibronectin in the co-cultures did not affect the eosinophil survival enhancing activity. Prednisolone inhibited the eosinophil survival enhancing activity of the co-cultures by suppression of GM-CSF production. Soluble eosinophil-derived cytokines are involved in the interaction of eosinophils with myofibroblasts, which results in a tumour necrosis factor-alpha/interleukin-1 alpha mediated release of granulocyte/macrophage colony-stimulating factor from myofibroblasts. Bronchial myofibroblasts can, thereby, contribute to allergic inflammation by granulocyte/macrophage colony-stimulating factor-mediated inhibition of eosinophil apoptosis.

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Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro
S Zhang, Q Mohammed, A Burbidge, CM Morland, WR Roche
European Respiratory Journal Sep 1996, 9 (9) 1839-1846;

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Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro
S Zhang, Q Mohammed, A Burbidge, CM Morland, WR Roche
European Respiratory Journal Sep 1996, 9 (9) 1839-1846;
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