INVOLVEMENT OF ENDOTHELIN IN MONONUCLEAR PHAGOCYTE INFLAMMATION IN ASTHMA

Background and aim: Endothelin has bronchoconstrictive, vasoactive, an d inflammatory properties and may be involved in the pathogenesis of a sthma. We have studied the involvement of endothelin in asthma by exam ining its expression and release by mononuclear phagocytes obtained fr om 56 patients with asthma and 32 control subjects and the activation of mononuclear phagocytes by endothelin.Methods: Endothelin immunoreac tivity was studied by using immunocytochemistry on monocytes and alveo lar macrophages. Spontaneous and lipopolysaccharide-induced endothelin release from monocytes and alveolar macrophages was studied by radioi mmunoassay. The proportion of intracellular endothelin was assessed af ter cell disruption by Triton (Union Carbide Corp., Bound Brook, N.J.) . The release of fibronectin and tumor necrosis factor-alpha induced b y 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 cont rol 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 inc reased the release of tumor necrosis factor-alpha and fibronectin by a lveolar macrophages from normal subjects and patients with stable asth ma, but it significantly decreased their release in patients with unst able asthma. Conclusion: This study suggests a role for endothelin in airway inflammation in asthma. Endothelin may act in a different fashi on on alveolar macrophages, depending on the degree of stability of th e disease.