Prolongation of discordant renal xenograft survival by depletion of complement. Comparative effects of systemically administered cobra venom factor and soluble complement receptor type 1 in a guinea-pig to rat model.
There is an increasing body of evidence to suggest that inhibition of complement activation may be a valuable approach to avert hyperacute rejection. In our study, the guinea-pig to rat discordant kidney xenograft model was adapted for the investigation of renal transplant function and an attempt was made to delay the hyperacute rejection using systemically administered cobra venom factor (CVF) and soluble complement receptor type 1 (sCR1). The saline-treated control recipients experienced a rapid transplant rejection with a xenograft survival averaging 10.5 +/- 2.1 min. Administration of a single 60 U/kg i.v. bolus of CVF significantly prolonged renal graft survival to 20.4 +/- 2.5 h, and by a single bolus of sCR1 (50 mg/kg) a prolongation of graft survival to 18.8 +/- 2.3 h was achieved. The grafts functioned only over periods of 2.5 +/- 0.3 and 2.3 +/- 0.2 h, respectively. No complications of sCR1 were noted. We concluded that complement inhibition by sCR1 may be an important component in the therapeutic approach aiming at the prevention of hyperacute rejection in human organ transplantation.
Department of Urology, University of Heidelberg, Germany.
M
M
Chrupcala
S
S
Pomer
G
G
Staehler
R
R
Waldherr
C
C
Kirschfink
D000818:Animals; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D003165:Complement System Proteins / Q000378:metabolism; D004546:Elapid Venoms / Q000494:pharmacology*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011951:Receptors, Complement / Q000627:therapeutic use*; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D011951:Receptors, Complement; C016310:cobra venom factor; D003165:Complement System Proteins