Dosanjh Amrita, Ikonen Tuija, Morris Randall
Transplant Immunology, Stanford University School of Medicine, Stanford, California, USA.
J Heart Lung Transplant. 2004 Apr;23(4):456-60. doi: 10.1016/S1053-2498(03)00206-7.
Obliterative bronchiolitis (OB) is the major cause of morbidity and mortality after lung transplantation. One initiating event in the development of obliteration of the airway lumen is epithelial injury. In our model of chronic rejection, initial ischemic injury and denudation of the epithelium occurs in the isografts, with eventual re-epithelialization and partial patency of the airway lumen. In contrast, allografts do not recover epithelium, and the airway lumen becomes obliterated. We hypothesized that because integrin alphaVbeta6 is expressed in healing epithelium, integrin alphaVbeta6 expression would be greatly increased in isografts, but not in allografts.
Using a rat tracheal allograft rejection model as a source of 4- to 5-microm tissue sections, we compared integrin staining in allografts vs isografts from animals at post-transplant Days 7, 14, 28, and 60. We analyzed the sections using immunohistochemistry after incubation with a specific monoclonal antibody E7P6 against integrin alphaVbeta6. Negative control slides were processed identically, except that primary antibody was omitted.
The sections from healing, re-epithelializing isografts showed intense staining when using the antibody recognizing integrin alphaVbeta6, compared with the allografts studied. Days 7 and 14 isografts had increased epithelial expression of alphaVbeta6. As the isograft epithelium recovered, the intensity diminished at Days 28 and 60. In allografts, at Days 7 to 60, we detected only a comparatively low-level of expression in injured epithelium.
Integrin alphaVbeta6 is readily detectable in healing isografts. Integrin alphaVbeta6 may be crucial in maintaining a viable epithelial cell layer, which is related to slowed progression of airway obliteration in OB.
闭塞性细支气管炎（OB）是肺移植后发病和死亡的主要原因。气道管腔闭塞发展过程中的一个起始事件是上皮损伤。在我们的慢性排斥模型中，同基因移植中最初会发生缺血性损伤和上皮剥脱，最终气道管腔会重新上皮化并部分通畅。相比之下，异基因移植不会恢复上皮，气道管腔会闭塞。我们推测，由于整合素αVβ6在愈合的上皮中表达，因此同基因移植中整合素αVβ6的表达会大幅增加，而异基因移植中则不会。
使用大鼠气管异基因移植排斥模型获取4至5微米的组织切片，我们比较了移植后第7、14、28和60天动物的异基因移植与同基因移植中的整合素染色情况。在用针对整合素αVβ6的特异性单克隆抗体E7P6孵育后，我们使用免疫组织化学分析切片。阴性对照玻片的处理方式相同，只是省略了一抗。
与所研究的异基因移植相比，使用识别整合素αVβ6的抗体时，愈合、重新上皮化的同基因移植切片显示出强烈染色。第7天和第1天的同基因移植中αVβ6的上皮表达增加。随着同基因移植上皮的恢复，在第28天和第60天强度减弱。在异基因移植中，在第7至60天，我们仅在受损上皮中检测到相对较低水平的表达。
整合素αVβ6在愈合的同基因移植中易于检测到。整合素αVβ6可能在维持存活的上皮细胞层方面至关重要，这与OB中气道闭塞进展减缓有关。
