The role of the beta chemokines in experimental obliterative bronchiolitis

• Published in: Experimental and molecular pathology Vol. 75; no. 3; pp. 210 - 216
• Main Authors: Farivar, Alexander S, Krishnadasan, Baiya, Naidu, Babu V, Woolley, Steven M, Mulligan, Michael S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2003; Elsevier
• Subjects: Animals; Antibodies - therapeutic use; Beta chemokines; Biological and medical sciences; Blotting, Northern; Bronchiolitis Obliterans - metabolism; Bronchiolitis Obliterans - prevention & control; Chemokine CCL2 - immunology; Chemokine CCL5 - immunology; Chemokines, CC - immunology; Chemokines, CC - metabolism; Chronic obstructive pulmonary disease, asthma; Disease Models, Animal; Graft Rejection - metabolism; Graft Rejection - pathology; Heterotopic tracheal transplantation; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Lung transplantation; Male; MCP-1; Medical sciences; Obliterative bronchiolitis; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pneumology; RANTES; Rat tracheal allografts; Rats; RNA, Messenger - analysis; Trachea - pathology; Trachea - transplantation; Transplantation, Homologous - immunology; Transplantation, Isogeneic - immunology; MCP-1; RANTES; Lung transplantation; Beta chemokines; Obliterative bronchiolitis; Rat tracheal allografts; Heterotopic tracheal transplantation; Respiratory disease; Experimental study; Bronchiolitis; Chemokine; Anatomic pathology; Bronchus disease
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/S0014-4800(03)00093-5

Beta chemokines have been implicated in cardiac and renal allograft rejection. This study determined if antibody antagonization of beta chemokines conferred protection against the development of experimental obliterative bronchiolitis (OB) in a heterotopic rat tracheal allograft model. Rat tracheas were transplanted from Brown-Norway or Lewis donors into Lewis recipients. Rats received 200 μg/day of either anti-RANTES or anti-MCP-1 antibody for 14 days. Luminal obstruction and epithelial loss were calculated. Northern blots for MCP-1 and RANTES mRNA expression were performed, and immunohistochemistry for chemokine protein localization. There was a significant increase in airway obstruction in allografts compared to isografts ( P < 0.001). Antibody-treated allografts demonstrated an amelioration of airway obstruction from 58% (vehicle allografts) to 26% (anti-RANTES) and 12% (anti-MCP-1), both of which were significant ( P < 0.001). Epithelial preservation was increased in both antibody-treated groups ( P < 0.001), and increased expression of MCP-1 and RANTES mRNA was present in tracheal allografts by Day 2 and maximal by Day 6. Beta chemokines are expressed during the development of experimental OB, as MCP-1 and RANTES mRNA expression increased with time from transplantation. Both MCP-1 and RANTES are functional in the formation of the fibroproliferative response that characterizes OB in this model, and their antagonization conferred protection against airway obstruction and epithelial loss.