气道上皮损伤在小鼠原位气管同种异体移植排斥反应中的作用。

Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

作者信息

Kuo Elbert, Bharat Ankit, Shih Jennifer, Street Tyler, Norris Jenyi, Liu Wei, Parks William, Walter Michael, Patterson G Alexander, Mohanakumar T

机构信息

Department of Surgery, Washington University, St. Louis, Missouri 63110, USA.

出版信息

Ann Thorac Surg. 2006 Oct;82(4):1226-33. doi: 10.1016/j.athoracsur.2006.03.122.

DOI:10.1016/j.athoracsur.2006.03.122

PMID:16996912

Abstract

BACKGROUND

Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection.

METHODS

Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts.

RESULTS

Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio.

CONCLUSIONS

Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

摘要

背景

小鼠气管移植是用于研究闭塞性细支气管炎综合征的一种模型，该综合征是肺移植后发病和死亡的主要原因。与小鼠异位气管移植不同，尽管主要组织相容性抗原不匹配，但原位移植不会导致管腔闭塞。受体来源的上皮细胞重新填充气管同种异体移植物可防止管腔闭塞。本研究的目的是确定：（1）原位气管移植是否显示同种异体移植排斥反应的迹象；（2）气道上皮细胞损伤是否促进原位气管同种异体移植排斥反应。

方法

进行了40例同基因（C57BL/6至C57BL/6）和40例异基因（BALB/c至C57BL/6）原位气管移植。通过仙台病毒（SdV）感染以及将气管移植到不能重新上皮化的基质金属蛋白酶-7基因敲除（MMP7-KO）受体小鼠中诱导气道上皮细胞损伤。在收获的同种异体移植物上借助计算机计算纤维化百分比和固有层与软骨的比例。