POSTTRANSPLANT NONFUNCTION OF CANINE ISLETS IN PVG RATS DEFICIENT IN COMPLEMENT COMPONENT C6

Background. Discordant islet xenografts are immediately nonfunctional in nonimmunosuppressed recipients other than the mouse, a process call ed primary nonfunction, Although at present it is unknown whether comp lement is involved, complement might participate in the induction of p rimary nonfunction through a number of mechanisms. We investigated the potential role of the membrane attack complex of complement in primar y nonfunction of transplanted xenoislets, Methods. Canine islets were transplanted into both nonimmunosuppressed and immunosuppressed normoc omplementemic and C6-deficient (C6D) PVG rats. Cyclosporine, rapamycin , deoxyspergualin, and myco-phenolate mofetil were used for immunosupp ression from day -3 to cessation of islet cell function. Serum glucose was measured at 6 hr after transplant and daily thereafter. Xenograft tissue sections were obtained at various times after transplant and s tained for inflammatory cells and insulin. Results. Canine islets graf ted in nonimmunosuppressed C6D rats and normocomplementemic rats under went primary nonfunction in all animals. The incidence of primary nonf unction in animals receiving a four-drug immunosuppressive regimen was 33% in the normocomplementemic rats but only 10% in the C6D rats. The mean functional islet survival time was 1.57+/-0.33 days in the normo complementemic group and 2.70+/-0.67 days in the C6D group (P=0.38), T he islet xenografts showed little difference in degree and composition of cell infiltration between normocomplementemic and C6D rats. Conclu sion. The membrane attack complex does not appear to play a major role in primary nonfunction of canine islet xenografts in nonimmunosuppres sed PVG rats. However, there was a lower incidence of primary nonfunct ion and a longer posttransplant survival time in immunosuppressed C6D rats, suggesting the membrane attack complex may play a minor role in recipients that are heavily immunosuppressed.