Anti-Macrophage Migration Inhibitory Factor Antibody Suppresses Chronic Rejection of Heterotopically Transplanted Trachea in Rats
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Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine essential for delayed hypersensitivity <I>in vivo</I>, and is involved in bronchiolitis obliterans and late rejection in lung transplantation. We tested here whether neutralization of MIF using anti-MIF antibody prevents such a response. We examined the MIF mRNA expression level and changes in allograft tracheal epithelium and intraluminal obstruction in a rat allograft model. Lewis rat (RT1<SUP>l</SUP>) underwent heterotopic tracheal transplantation from Brown Norway rats (RT1<SUP>n</SUP>) in the omentum. Anti-MIF antibody was injected in the peritoneum. Rats were divided into three groups (non-treated allograft, allograft treated with normal rabbit IgG and allograft treated with anti-MIF antibody). Implants were harvested on days 7 or 21 for histological analysis. MIF mRNA expression was higher in the allograft at days 7 and 21 than in the isograft. The epithelium in non-treated allograft was almost absent at day 7. The epithelial height in the anti-MIF-treated graft was higher than that in normal IgG-treated grafts. The intraluminal space was mostly replaced by granulation tissue at day 21 in the untreated group. The proportion of obliterans was lowest in the anti-MIF group, the second lowest in the untreated group and the third lowest in the normal IgG-treated grafts, and the difference was significant (<I>p</I><0.001) between the first two groups. Our results indicate that anti-MIF antibody suppresses allogenic tracheal rejection.
- 長崎大学医学部の論文
長崎大学医学部 | 論文
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