Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium
Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium
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DOI：
10.1001/archotol.129.1.118
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发表时间：
2003-01-01
影响因子：
--
通讯作者：
Mayer, L
中科院分区：
文献类型：
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作者：
Genden, EM;Iskander, AJ;Mayer, L
背景：异位异体气管移植排斥反应的特征是气道完全闭塞，而同种异体气管移植排斥反应导致气道水肿和固有层细胞浸润，但与气道闭塞无关。我们假设原位气管同种异体移植物经历了受体来源的粘膜的再上皮化，并且这一过程可以防止气道闭塞。方法：30只小鼠随机分为6个实验组。将BALB/c供体气管段原位或异位移植到同基因BALB/c或主要组织相容性不匹配的异体C57BL/6受体中。同种异体移植物受体分为非免疫抑制组和免疫抑制组（环孢素，7 mg/kg / d）。移植21天后，对移植物进行组织学评估、CD4和CD8淋巴细胞浸润免疫组化和主要组织相容性特异性免疫组化，以评估排斥反应和供体或受体组织来源。结果：未治疗的异位同种异体移植物在第21天完成气道完全闭塞。这种反应被环孢素免疫抑制所阻止。然而，未经治疗的同种异体原位移植物表现为水肿和固有层淋巴细胞浸润，导致临床喘鸣，没有气道闭塞。免疫抑制的同种异体原位移植物没有发生水肿或固有层浸润，因此没有发生喘鸣。免疫组织化学分析显示，在未治疗组和治疗组中，受体来源的粘膜都向供体同种异体移植物段迁移。结论：异位异体气管移植不具有排斥性气管阻塞的特征。在同种异体原位移植物中，受体粘膜向供体移植物的迁移似乎可以防止气道闭塞。这些结果表明，与传统的异位模型相比，原位气管移植模型更准确地反映了临床同种异体气管移植的生物学行为。
Background: While the rejection of heterotopic tracheal allografts is characterized by complete airway obliteration, the rejection of orthotopic allografts leads to airway edema and cellular infiltrate of the lamina propria, but is not associated with obliteration. We hypothesized that orthotopic tracheal allografts undergo reepithelialization with recipient-derived mucosa and that this process prevents airway obliteration.Methods: Thirty mice were randomly assigned to 6 experimental groups. BALB/c donor tracheal segments were transplanted orthotopically or heterotopically into syngeneic BALB/c or major histocompatability mismatched allogeneic C57BL/6 recipients. Recipients of allogeneic grafts were divided into a nonimmunosuppression group and an immunosuppression group (cyclosporine, 7 mg/kg per day). Twenty-one days after transplantation, histological assessment, immunohistochemistry for CD4 and CD8 lymphocyte infiltration and major histocompatibility-specific immunohistochemistry were performed on the grafts to assess rejection and donor or recipient origin of tissue.Results: Untreated heterotopic allografts underwent complete airway obliteration by day 21. This response was prevented with cyclosporine immunosuppression. Untreated orthotopic allografts, however, demonstrated edema and lymphocytic infiltrate of the lamina propria resulting in clinical stridor without airway obliteration. Immunosuppressed orthotopic allografts did not develop edema or infiltrate of the lamina propria and consequently stridor did not occur. Immunohistochemical analysis demonstrated migration of recipient-derived mucosa into the donor allograft segment in both the untreated and treated orthotopic groups.Conclusions: Airway obliteration characteristic of rejecting heterotopic tracheal allografts does not occur in the orthotopic allografts. Migration of recipient mucosa into the donor allograft appears to prevent airway obliteration in the orthotopic allografts. These findings suggest that the orthotopic tracheal transplantation model more accurately represents the biological behavior of clinical tracheal allografts than the traditional heterotopic model.