CELL-CULTURES FROM BRONCHIAL SUBEPITHELIAL MYOFIBROBLASTS ENHANCE EOSINOPHIL SURVIVAL IN-VITRO

Mechanisms of eosinophil accumulation and activation in the bronchial mucosa are crucial for the pathogenesis of asthma. The location of spe cialized fibroblasts, myofibroblasts, beneath the bronchial basement m embrane and their proximity to infiltrating eosinophils potentially en able the myofibroblasts to modulate South Block eosinophil survival an d function in asthma. The aim of this study was to investigate the eff ects of bronchial myofibroblasts on eosinophil survival in vitro. Eosi nophils from human peripheral blood were exposed to cell cultures from bronchial myofibroblasts and to myofibroblast-conditioned media. Eosi nophil viability was assessed and granulocyte/macrophage colony-stimul ating factor (GM-CSF) production was examined in co-culture supernatan ts and as messenger ribonucleic acid (mRNA) in myofibroblasts. Eosinop hil survival was significantly increased and eosinophil apoptosis was inhibited by co-culture with myofibroblasts. Conditioned medium from t umour 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 increase d in co-cultures and by eosinophil-conditioned medium, Addition of ant ibodies to TNF-alpha and interleukin-1 alpha (IL-1 alpha) to co-cultur es resulted in significant reduction both in eosinophil survival and G M-CSF levels. Blocking of fibronectin in the cocultures did not affect the eosinophil survival enhancing activity, Prednisolone inhibited th e eosinophil survival enhancing activity of the co-cultures by suppres sion of GM-CSF production. Soluble eosinophil-derived cytokines are in volved in the interaction of eosinophils with myofibroblasts, which re sults in a tumour necrosis factor-alpha/interleukin-1 alpha mediated r elease of granulocyte/macrophage colony-stimulating factor from myofib roblasts, Bronchial myofibroblasts can, thereby, contribute to allergi c inflammation by granulocyte/macrophage colony-stimulating factor-med iated inhibition of eosinophil apoptosis.