REJECTION MECHANISM AND IMMUNOSUPPRESSIVE STRATEGY OF SMALL BOWEL TRANSPLANTATION.
REJECTION MECHANISM AND IMMUNOSUPPRESSIVE STRATEGY OF SMALL BOWEL TRANSPLANTATION.
批准号:
09671835
负责人:
KANEHIRO Hiromichi
金额:
$1.6万
依托单位:
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
项目状态:
已结题
起止时间:
1997 至 1999
中文摘要
p38丝裂原活化蛋白激酶(MAPK)是一种负责转导炎症信号的应激激活酶。在CD8+ T淋巴细胞上,p38的表达与细胞毒活性相关。在凋亡信号通路中,p38被TNF-α激活,激活p38可诱导细胞凋亡。方法。行异位小肠移植(SBT)。Group1。LEW→LEW (n=3), Group2。BN→LEW (n=5,未处理),第3组,BN→LEW (n=3, FK506 0.5 mg/kg, ig给药7 d)。第4组BN→LEW (n=3,抗tnf -α抗体;1.0mg/kg,腹腔注射)。对p38和磷酸特异性p38进行组织学、细胞凋亡、免疫染色和Western blot检测。结果。第1组移植后第7天的组织病理学结果,第2组出现中度至重度排斥反应。另一方面,第3组和第4组在移植后第7天出现轻至中度排斥反应。2组CD8a/p38双阳性细胞的移植物浸润量较3组明显增加。Mann-Whitney u检验tunel - 10 HPF阳性细胞2组(9.4±3.6)个比1组(0.7±0.6)个多(p=0.024)。4组阳性细胞数(4.3±1.5)个,较2组明显减少(p=0.047)。四组间表达p38的细胞数量无显著差异。在磷酸化特异性p38的表达上,2组阳性细胞数明显多于4组。免疫印迹法检测排斥同种异体移植物中磷酸特异性p38的免疫反应条带2组明显强于4组。结论。由于同种异体移植排斥反应的浸润细胞主要表达磷特异性p38,因此FK506和抗tnf抗体联合治疗可能通过抑制p38的激活而成功。
英文摘要
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.
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