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 microg/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.