Am. J. Respir. Crit. Care Med., Volume 162, Number 5, November 2000, 1940-1948

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

MICHIHARU SUGA, ALEXANDRA A. MACLEAN, SHAF KESHAVJEE, STEFAN FISCHER, JORGE M. F. MOREIRA, and MINGYAO LIU

Thoracic Surgery Research Laboratory, Toronto General Hospital Research Institute, and Department of Surgery, University of Toronto, Toronto, Ontario, Canada

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.

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