RANTES plays an important role in the evolution of allograft transplant-induced fibrous airway obliteration

Although lung transplantation is a widely applied therapeutic modality for end-stage pulmonary disease, the long-term survival following this procedur e is limited by the development of bronchiolitis obliterans (BO). We invest igated the role of RANTES, a C-C chemokine, in the evolution of fibrous air way obliteration (FAO) using a rat heterotopic tracheal transplant model. R ANTES was highly expressed in infiltrating mononuclear cells in both alloge neic and isogeneic grafts as revealed by immunohistochemistry. Using a mini osmotic pump, neutralizing anti-RANTES antibody was locally and continuousl y infused to allografts, whereas recombinant rat RANTES was administered to isografts. Anti-RANTES antibody treatment decreased the number of CD4(+) i nfiltrating cells in allotracheas and preserved luminal patency compared wi th those of allocontrols, However, RANTES infusion in isografts did not ind uce 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 administratio n of anti-RANTES might be a therapeutic option for BO following lung transp lantation.