Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro

Abstract

C Ce el ll l c cu ul lt tu ur re es s f fr ro om m b br ro on nc ch hi ia al l s su ub be ep pi it th he el li ia al l m my yo of fi ib br ro ob bl la as st ts s e en nh ha an nc ce e e eo os si in no op ph hi il l s su ur rv vi iv va al l i in n v vi it tr ro o 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-α (TNF-α)-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-α and interleukin-1α (IL-1α) 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-α/interleukin-1α 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.

Granulocyte macrophage colony-stimulating factor is the main cytokine enhancing survival of eosinophils in asthmatic airways

“…Eosinophils also produce IL-5 and GM-CSF [26]. Bronchial myofibro-blasts prolong eosinophil survival by tumour necrosis factor-α and IL-1-mediated synthesis of GM-CSF [27]. The ESEA correlated with the percentage of eosinophils of BAL cells, but not with those of other inflammatory cells.…”

Selective Phosphodiesterase Type 4 Inhibitors Reduce the Prolonged Survival of Eosinophils Stimulated by Granulocyte-Macrophage Colony-Stimulating Factor.

“…3,4) Since eosinophils are selectively accumulated in the bronchial mucosa of asthmatic patients, 22) it would be expected that local tissue factors play a major role in the prolonged survival and activation of eosinophils, which lead to increases in their inflammatory effects. Recent in vitro studies by Zhang and colleagues 23) reported that bronchial myofibroblasts prolonged the survival of human peripheral blood eosinophils. They also demonstrated that GM-CSF induced the prolonged survival of eosinophils, but IL-5 did not.…”

Eosinophil Activation of Fibroblasts from Chronic Allergen-Induced Disease Utilizes Stem Cell Factor for Phenotypic Changes

“…Previous studies have indicated that eosinophils can contribute significantly to myofibroblast differentiation. 27,28 Eosinophils store and release several fibrogenic factors, such . Anti-SCF antibodies inhibited eosinophil-induced TGF-␤ expression by CRA fibroblasts.…”

“…27,28 To examine this aspect we assessed ␣-SMA, which is the primary indication for myofibroblast differentiation. At baseline CRA fibroblasts exhibited significantly higher ␣-SMA mRNA expression level ( Figure 4A) and protein production ( Figure 4B) compared to fibroblasts from naive animals.…”