同种异体啮齿动物小肠移植中的急性排斥反应通过肠肌层内的炎症反应导致平滑肌功能障碍。

Acute rejection in allogeneic rodent small bowel transplantation causes smooth muscle dysfunction via an inflammatory response within the intestinal muscularis.

作者信息

Schaefer N, Tahara K, Websky M v, Kalff J C, Hirner A, Türler A

机构信息

Department of Surgery, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.

出版信息

Transplant Proc. 2006 Jul-Aug;38(6):1792-3. doi: 10.1016/j.transproceed.2006.05.047.

DOI:10.1016/j.transproceed.2006.05.047

PMID:16908282

Abstract

INTRODUCTION

Isogeneic intestinal transplantation elicits an inflammatory response within the intestinal muscularis that is associated with dysmotility. Usually the inflammation and the postoperative motor dysfunction resolve within a few days after small bowel transplantation (SBTx). However, the onset of acute rejection in allogeneic SBTx is again associated with dysmotility. We hypothesized that dysmotility during acute rejection is based on coexpression of kinetically active mediators by the alloreactive leucocyte infiltrate.

MATERIALS AND METHODS

Rat SBTx (BN to Lew and BN to BN) was performed without immunosuppression. Animals were sacrificed at 1, 4, and 7 days after SBTx. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by reverse transcriptase polymerase chain reaction. Muscle contractility was assessed in a standard organ bath.

RESULTS

Transplanted animals showed a significant inflammatory response within the muscularis at day 1 after SBTx. However, allogeneic transplanted animals exhibited a significant second inflammatory peak at day 7 (mRNA induction: iNOS 150-fold; tumor necrosis factor-alpha 18-fold; interferon-gamma 397-fold), parallel to the onset of rejection. This change was associated with a significant leukocyte infiltration. Compared to controls, allogeneic transplanted animals showed a 29% decrease in smooth muscle contractility on days 1 and 4 and a 71% decrease of contractility on postoperative day 7.

CONCLUSIONS

The motor dysfunction of transplanted small bowel during acute rejection is associated with an inflammatory reaction in the intestinal muscularis. The initial unspecific inflammation process immediately after transplantation is reactivated and intensified during acute rejection.

摘要

引言

同基因肠道移植会在肠肌层引发炎症反应，这与运动功能障碍有关。通常，小肠移植（SBTx）后几天内炎症和术后运动功能障碍会消退。然而，同种异体SBTx中急性排斥反应的发生再次与运动功能障碍相关。我们推测急性排斥反应期间的运动功能障碍是基于同种反应性白细胞浸润共同表达具有动力学活性的介质。

材料与方法

在不进行免疫抑制的情况下进行大鼠SBTx（从BN到Lew和从BN到BN）。在SBTx后1、4和7天处死动物。通过免疫组织化学研究肌层整装片中的白细胞浸润情况。通过逆转录聚合酶链反应测定介质mRNA表达。在标准器官浴中评估肌肉收缩力。

结果

移植动物在SBTx后第1天肌层内出现显著的炎症反应。然而，同种异体移植动物在第7天出现显著的第二个炎症高峰（mRNA诱导：诱导型一氧化氮合酶150倍；肿瘤坏死因子-α 18倍；干扰素-γ 397倍），与排斥反应的发生同时出现。这种变化与显著的白细胞浸润相关。与对照组相比，同种异体移植动物在第1天和第4天平滑肌收缩力下降29%，术后第7天收缩力下降71%。