Immunohistochemical localization of endothelin-1 and endothelin-converting enzyme-1 in rat lung allografts

Chronic rejection is one of the principal factors that lead to development of obliterative bronchiolitis, which is the cause of death for 50% of lung allograft recipients. To more fully comprehend the pathogenesis of chronic rejection, we investigated the expression of endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1) in inadequately immuno-suppressed rat lung allografts (n = 15) at monthly intervals after transplantation and compared these findings with those in normal rat lung (n = 5), using immunohistochemistry. Throughout the posttransplantation period, inflammatory cells expressed weak to moderate immunoexpression for both peptides. Constant weak to moderate immunoexpression for both peptides was also seen in the alveolar epithelium and neovascularized endothelium. Early after transplantation the vascular endothelium demonstrated strong immunostaining compared with control sections. This immunostaining, however, was reduced to control levels at later stages of rejection. As rejection progressed, staining in the airway epithelium diminished to weak levels as compared with that in controls. These findings suggest a causal role for ET-1 and ECE-1 in the inflammatory and proliferative damage associated with chronic rejection after lung transplantation.