REJECTION MECHANISM AND IMMUNOSUPPRESSIVE STRATEGY OF SMALL BOWEL TRANSPLANTATION.

小肠移植的排斥机制和免疫抑制策略。

• 批准号: 09671835
• 负责人: KANEHIRO Hiromichi
• 金额: $ 1.6万
• 依托单位: NARA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671835/
• 关键词: small bowel transplantation; mitogen-activated protein kinase; p38; TNF-α; 拒絶反応; p38MAPK; 特異的免疫抑制法; 細胞分離

The p38 mitogen-activated protein kinase (MAPK) is a stress-activated enzyme responsible for transducing inflammatory signals. On CD8+ T lymphocytes, p38 expression correlates with cytotoxic activity. Concerning apoptotic signaling pathways, p38 is activated by TNF-α and activation of p38 may induce apoptosis. Methods. Heterotopic small bowel transplantation (SBT) was performed. Group1. LEW → LEW (n=3), Group2. BN → LEW (n=5, no treatment), Group3, BN → LEW (n=3, FK506 0.5 mg/kg, i.m.for 7 days). Group4 BN → LEW (n=3, anti-TNF-α antibody ; 1.0mg/kg, i.p.injection at SBT). Histology, apoptosis, immunostaining of p38 and phosphospecific p38, and Western blot of phosphospecific p38 were examined. Results. The histopathologic findings of Group 1 on day 7 after transplantation, moderate to serve rejection was observed in Group 2. On the other hand, Group 3 and 4 on day 7 after transplantation showed mild to moderate rejection. The graft infiltrating CD8a/p38-double positive cells in Group 2 significantly increased compared with Group3. Concerning TUNEL-positive cells 10 HPF by Mann-Whitney U-test, there were more positive cells in Group 2 (9.4±3.6) than in Group 1 (0.7±0.6) (p=0.024). However, the number of positive cells in Group 4 (4.3±1.5) decreased significantly compared with Group 2 (p=0.047). There was no significant difference in the number of cells expressing p38 among four groups. In expression of phosphospecific p38, the numbers of positive cells in Group 2 seemed like more than that in Group 4. In the western blotting of phosphospecific p38 in rejecting allografts, immunoreactive bands in Group 2 were detected stronger than that in Group 4. Conclusions. Since the infiltrating cells at allograft rejection would predominantly express phosphospecific p38, combined FK506 and anti-TNF antibody therapy might success by suppressing the activation of p38.

p38有丝分裂原激活的蛋白激酶（MAPK）是导致炎症信号的AS-ACTIVAVAVE，P38表达与细胞毒性活性相关。进行异位小肠移植（SBT）。 ，抗TNF-α抗体；在p38和磷酸体p38的p38中，p38的p38染色。另一方面，移植后第3和4天的第7天显示了与第2组相比，第2组中的移植物浸润CD8A/P38双阳性细胞显着增加。惠特尼U检验，第2组（9.4±3.6）中有更多的阳性细胞（0.7±0.6）（p = 0.024）。在第4组中表达p38的细胞数量。主要表达磷酸p38 506和抗TNF抗体疗法可能通过抑制p38的激活而成功。