Involvement of endothelin in mononuclear phagocyte inflammation in asthma

Background and aim: Endothelin has bronchoconstrictive, vasoactive, and inflammatory properties and may be involved in the pathogenesis of asthma. We have studied the involvement of endothelin in asthma by examining its expression and release by mononuclear phagocytes obtained from 56 patients with asthma and 32 control subjects and the activation of mononuclear phagocytes by endothelin. Methods: Endothelin immunoreactivity was studied by using immunocytochemistry on monocytes and alveolar macrophages. Spontaneous and lipopolysaccharide-induced endothelin release from monocytes and alveolar macrophages was studied by radioimmunoassay. The proportion of intracellular endothelin was assessed after cell disruption by Triton (Union Carbide Corp., Bound Brook, N.J.). The release of fibronectin and tumor necrosis factor-alpha induced by endothelin was studied in alveolar macrophages by enzyme immunoassay. Results: Endothelin immunoreactivity was significantly increased in cells from patients with asthma in comparison with those from the control group, but its release by alveolar macrophages was similar in both groups. Levels in the cell lysates and supernatants were similar for patients with asthma and normal subjects. Endothelin significantly increased the release of tumor necrosis factor-alpha and fibronectin by alveolar macrophages from normal subjects and patients with stable asthma, but it significantly decreased their release in patients with unstable asthma. Conclusion: This study suggests a role for endothelin in airway inflammation in asthma. Endothelin may act in a different fashion on alveolar macrophages, depending on the degree of stability of the disease.