Kenyon N S, Strasser S, Alejandro R
Diabetes Research Institute, Miami, Florida 33101.
Diabetes. 1990 Mar;39(3):305-11. doi: 10.2337/diab.39.3.305.
Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100.(ABSTRACT TRUNCATED AT 250 WORDS)
在啮齿动物模型中,已证明对供体胰岛进行紫外线(UV)照射可有效延长胰岛同种异体移植的存活时间。本研究评估了紫外线作为犬胰岛免疫调节剂的作用。紫外线照射对体外胰岛分泌功能的影响显示,随着紫外线剂量增加,基础胰岛素释放呈增加趋势,而从紫外线照射剂量为200 - 300 J/m²开始,葡萄糖介导的胰岛素释放(以基础胰岛素释放分数的百分比表示)相应显著降低(n = 3,P < 0.05)。在29个混合淋巴细胞培养物中的27个以及5个混合淋巴细胞胰岛培养实验中的4个中,对紫外线照射的同种异体外周血白细胞和胰岛的增殖反应分别从200 - 600 J/m²开始显著降低53 - 112%(P < 0.05)和35 - 74%(P < 0.05)。未照射(n = 8)和照射(600 J/m²,n = 6)胰岛的自体移植导致对照组1个月移植存活率为75%,照射组为50%。将照射(600 J/m²)的胰岛同种异体移植到未免疫抑制的受体(1个供体对1个受体,n = 8)或接受亚免疫抑制剂量环孢素的受体(2个供体对1个受体,n = 4)中,到第10天时均100%发生排斥。相比之下,当胰岛在照射后培养24小时并移植到环孢素处理的胰腺切除受体(2个供体对1个受体)中时,7个移植物中有3个存活时间延长至第10天以后,分别为第16天、第26天和大于100天。(摘要截短于250字)