Impact of Cobra Venom Factor on Immunologic Reaction in Rat Xenograft

Han, Duck Jong; Kim, Song Cheol; Jang, Hyuk Jae; Wee, Yu Mee; Lee, Jang Hyuk; Park, Hee Yung; Yu, Eun Sil

Abstract

Recently xenotransplantation has been thought as a final solution for the controi of donor organ shortage in allograft. In order to be a ciinicai entity, xenotransplantation has many obstacles such as hyperacute rejection and delayed xenogratt rejection as a potent immunologic reaction, zoonosis and ethical problems. We already reported the eariy immunoiogic events occuring soon after xenograft in animal model, in which natural antibody and complement have a crucial roie in rejection response. As a further step for the prolongation of graft survival, we used anticomplement agent (cobra venom factor, CVF) in the same model. Graft survival in discordant (guinea pig-to-rat) xenogratt was extended from 30.6 minutes to 2 days following singie injection of CVF, which showed similar pattern of rejection with the concordant xenogratt in terms of time of rejection response after grafting. In this setting antibody response in the blood did not show any difference between that of pre CVF and post CVF, even though IgM response was more pronounced than IgG. The complement activity in the blood showed marked suppression following CVF injection. Intragraft complement gene (C3 mRNA) expression in CVF injected discordant showed delayed response in a similar pattern like that of concordant xenograft. Interestingly enough intragraft anticomplement gene expression showed the simiiar pattern of response with the complement. From these results we can conclude that anticomplement agent (CVF) extended the graft survival in discordant xenograft upto the level of concordant xenograft by shifting the complement activation response from that of discordant to concordant xenograft.