Posttransplant nonfunction of canine islets in PVG rats deficient in complement component C6.
Posttransplant nonfunction of canine islets in PVG rats deficient in complement component C6.
复制标题
缺乏补体成分 C6 的 PVG 大鼠中犬胰岛移植后无功能。
DOI：
10.1097/00007890-199806270-00003
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发表时间：
1998
期刊：
影响因子：
6.2
通讯作者：
Dalmasso,AP
中科院分区：
文献类型：
--
作者：
Kronson,JW;Hering,BJ;Sutherland,DE;Tanioka,Y;Leone,JP;Kirchhof,N;Dalmasso,AP
背景。不协调胰岛异种移植物在除小鼠以外的非免疫抑制受体中立即丧失功能，这一过程称为原发性丧失功能。虽然目前尚不清楚补体是否参与其中，但补体可能通过多种机制参与了原发性失功能的诱导。方法将犬胰岛移植于无免疫抑制和免疫抑制的正常补体和c6缺陷（C6D） PVG大鼠。从第3天到胰岛细胞功能停止，使用环孢素、雷帕霉素、脱氧spergualin和霉酚酸酯进行免疫抑制。移植后6小时测定血清葡萄糖，此后每天测定一次。结果：非免疫抑制C6D大鼠和正常补体大鼠移植的犬胰岛均出现原发性无功能。在接受四种药物免疫抑制方案的动物中，正常补体大鼠的原发性无功能发生率为33%，而C6D大鼠仅为10%。正常补体组的平均功能胰岛生存时间为1.57±0.33天，C6D组的平均功能胰岛生存时间为2.70±0.67天（P= 0.38）。结论：膜攻击复合物在非免疫抑制PVG大鼠移植犬胰岛的原发性功能丧失中似乎不是起主要作用。然而，免疫抑制的C6D大鼠原发性无功能发生率较低，移植后存活时间较长，表明膜攻击复合物可能在免疫严重抑制的受体中起次要作用。
Background.Discordant islet xenografts are immediately nonfunctional in nonimmunosuppressed recipients other than the mouse, a process called primary nonfunction. Although at present it is unknown whether complement is involved, complement might participate in the induction of primary nonfunction through a number of mechanisms. We investigated the potential role of the membrane attack complex of complement in primary nonfunction of transplanted xenoislets.Methods.Canine islets were transplanted into both nonimmunosuppressed and immunosuppressed normocomplementemic and C6-deficient (C6D) PVG rats. Cyclosporine, rapamycin, deoxyspergualin, and mycophenolate mofetil were used for immunosuppression 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 stained for inflammatory cells and insulin.Results.Canine islets grafted in nonimmunosuppressed C6D rats and normocomplementemic rats underwent primary nonfunction in all animals. The incidence of primary nonfunction 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 normocomplementemic group and 2.70±0.67 days in the C6D group (P= 0.38). The islet xenografts showed little difference in degree and composition of cell infiltration between normocomplementemic and C6D rats.Conclusion.The membrane attack complex does not appear to play a major role in primary nonfunction of canine islet xenografts in nonimmunosuppressed PVG rats. However, there was a lower incidence of primary nonfunction 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.