Activated eosinophils stimulate endothelin-1 release from airway epithelial cells by direct adherence via adhesion...

Endothelin-1 (ET-1), synthesized in airway epithelial cells, has a potent constrictive action on airway smooth muscle. In this study, we investigated the effect of eosinophils on ET-1 release from guinea pig cultured tracheal epithelial cells. Eosinophils with or without the activation were directly co-cultured with tracheal epithelial cells. Eosinophils activated by GM/CSF or IL-5 potentiated ET-1 release, but non-activated ones did not. Treatment of activated eosinophils with antibodies against macrophage-1 (Mac-1) and/or very late antigen-4 (VLA-4) suppressed the potentiated ET-1 release. However, inhibition of lipid mediators derived from activated eosinophils could not suppress the potentiated ET-1 release. Moreover, separated co-culture of activated eosinophils with tracheal epithelial cells using Millicell-CM had no effect on ET-1 release. These observations suggest that adherence of activated eosinophils to epithelial cells via adhesion molecules such as Mac-1 and VLA-4 was essential for potentiation of ET-1 release. Since presence of eosinophils in the epithelial layer has been commonly demonstrated in bronchial biopsies and autopsy specimens from patients with asthma, epithelial cells would be activated by adherence of eosinophils via adhesion molecules and potentiate ET-1 release in vivo.