STRATEGY TO CONTROL XENOGRAFT REJECTION,AND POTENTIAL BENEFITS TO APPLY MHC-DEFICIENT DONOR

控制异种移植排斥的策略以及应用 MHC 缺陷供体的潜在益处

• 批准号: 06671184
• 负责人: OCHIAI Takenori
• 金额: $ 1.28万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06671184/
• 关键词: leukotrien B4; MHC; xenograft; FK506

Treatment with leukotrien B4 (LTB4) antagonist (50mg/kg) alone failed to prolong allograft survival, and combination of LTB4 antagonist and FK506 (0.32mg/kg) did not work in allograft model. Mouse skin graft on rats treated with LTB4 antagonist survived 11.5days, while xenograft on untreated rats were reiected in 8 days. Combination of LTB4 antagonist and suboptimal dose of FK brought 14.5 day-graft survival, while MST of FK alone group was 9.5 days. In the CML analysis, pig-effectors stimulated with B10.BR (H-2^k) killed B10.BR,C3H/HeJ (H-2^k) B10.A (4R) (sharing K^k with B10.BR) and C3H-KBR (sharing D^k with B10.BR) targets, respectively ; however killing activity was not shown on C57BL/10 (H-2^b) and C3H.SW(H-2^b) targets.In conclusion, LTB4 antagonist improved mouse skin graft survival on rats. This finding may support that neutrophile play a role in xenogeneic immune responses. Pig effectors recognize mouse class-I antigens and show killing activities on mouse targes. It may be expected that deletion of MHC antigens in xenograft might provide elongation of xenograft survival through the suppression of cellular responses.

单独应用白三烯B_4（LTB_4）拮抗剂（50 mg/kg）不能延长移植物存活时间，LTB_4拮抗剂与FK 506（0.32mg/kg）联合应用也不能延长移植物存活时间。小鼠皮肤移植物在LTB_4拮抗剂处理的大鼠上存活11.5天，而在未处理的大鼠上的异种移植物在8天内被排斥。LTB_4拮抗剂与次优剂量FK联合应用可使移植物存活14.5天，而单用FK组的MST为9.5天。在CML分析中，用B10.BR（H-2^k）刺激的猪效应器杀死B10.BR，C3 H/HeJ（H-2^k）B10.A（4 R）。（与B10.BR共享K^k）和C3 H-KBR（与B10.BR共享D^k）目标;然而，对C57 BL/10（H-2 μ b）和C3H.SW（H-2 μ b）靶没有显示杀伤活性。这一发现可能支持中性粒细胞在异种免疫反应中发挥作用。猪效应子识别小鼠I类抗原并对小鼠靶点显示杀伤活性。可以预期，异种移植物中MHC抗原的缺失可以通过抑制细胞反应来延长异种移植物的存活。

项目成果

Nakajima K,Ochiai T,and Isono K: "Method of heterotopic cardiac transplantation in rat model, -cuff method-" Organ Biology (in Japanese). 2. 61-66 (1995)

Nakajima K、Ochiai T 和 Isono K：“大鼠模型异位心脏移植方法，-袖带法-”器官生物学（日语）。

坂本薫: "異種移植免疫反応モデルとしての37℃ヒト全血によるミニブタ肝灌流の試み" Organ Biology. 1. 71-72 (1995)

坂本薰：“用37℃人全血进行小型猪肝脏作为异种移植免疫反应模型的试验”《器官生物学》1. 71-72 (1995)。

坂本 薫: "異種移植免疫反応モデルとしての37℃ヒト全血によるミニブタ肝灌流の試み" Organ Biology. 1. 71-72 (1995)

坂本薰：“用37℃人全血进行小型猪肝脏作为异种移植免疫反应模型的试验”《器官生物学》1. 71-72 (1995)。

坂本 薫: "異種移植免疫反応モデルとしての37℃ヒト全血によるミニブタ肝灌流の試み." Organ Biology. 1. 71-72 (1995)

Kaoru Sakamoto：“用 37℃ 人全血进行小型猪肝脏作为异种移植免疫反应模型的试验。” 1. 71-72 (1995)。