RANTES Plays an Important Role in the Evolution of Allograft Transplant-induced Fibrous Airway Obliteration

Abstract

Although lung transplantation is a widely applied therapeutic modality for end-stage pulmonary disease, the long-term survival following this procedure is limited by the development of bronchiolitis obliterans (BO). We investigated the role of RANTES, a C-C chemokine, in the evolution of fibrous airway obliteration (FAO) using a rat heterotopic tracheal transplant model. RANTES was highly expressed in infiltrating mononuclear cells in both allogeneic and isogeneic grafts as revealed by immunohistochemistry. Using a miniosmotic pump, neutralizing anti-RANTES antibody was locally and continuously infused to allografts, whereas recombinant rat RANTES was administered to isografts. Anti-RANTES antibody treatment decreased the number of CD4(+) infiltrating cells in allotracheas and preserved luminal patency compared with those of allocontrols. However, RANTES infusion in isografts did not induce FAO, even though CD4(+) cell migration was increased by this treatment. It appears that RANTES is relevant to the recruitment of CD4(+) cells and the development of FAO in the process of allorejection. Local administration of anti-RANTES might be a therapeutic option for BO following lung transplantation.