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 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.
Suga
M
M
Thoracic Surgery Research Laboratory, Toronto General Hospital Research Institute, and Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Maclean
A A
AA
Keshavjee
S
S
Fischer
S
S
Moreira
J M
JM
Liu
M
M
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000503:physiopathology*; D018791:CD4 Lymphocyte Count; D018946:Chemokine CCL5 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D000906:Antibodies; D018946:Chemokine CCL5; D011994:Recombinant Proteins