STRUCTURAL ALTERATIONS OF AIRWAY EPITHELIAL TIGHT JUNCTIONS IN CYSTIC-FIBROSIS - COMPARISON OF TRANSPLANT AND POSTMORTEM TISSUE

STRUCTURAL ALTERATIONS OF AIRWAY EPITHELIAL TIGHT JUNCTIONS IN CYSTIC-FIBROSIS - COMPARISON OF TRANSPLANT AND POSTMORTEM TISSUE
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DOI:
10.1165/ajrcmb/9.2.148
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发表时间:
1993-08-01
影响因子:
6.4
通讯作者:
JEFFERY, PK
JEFFERY, PK
中科院分区:
医学1区
文献类型:
--
作者:
GODFREY, RWA;SEVERS, NJ;JEFFERY, PK

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先前的描述性冷冻断裂研究表明,囊性纤维化(CF)中的气道上皮细胞与紧密连接元件的增殖和基底延伸相关。这些报告在CF中的意义一直难以评估,因为紧密连接是不稳定的结构,能够改变,死后。本研究的目的是测试的假设,即在紧密连接结构的异常先前报道的CF气道是独特的,并确定死后自溶的混杂效应。为此,我们分析了以下人气道上皮紧密连接:(1)从肺肿瘤切除的肺中取出的组织学正常组织(即,切除对照),(2)来自死于非呼吸原因的患者的肺(即,死后对照),(3)从进行移植的CF患者中取出的肺,和(4)来自死后CF患者的肺。分析了紧密连接深度、链数和连接复杂性。基底扩展和孤立的病灶的紧密连接元件被发现在所有组中,除了切除对照。因此,评估了以下两个参数:(1)连接延伸到切除对照中发现的最大深度以下的次数,以及(2)分离并远离顶外侧连接带的连接元件的范围。CF移植组、对照组和CF死后组的交界延伸超过正常最大值的平均发生率分别为4.8%、23.6%和48.8%。CF移植组、对照尸检组和CF尸检组构成孤立病灶的股长度与顶端紧密连接带长度的比值分别为4.6:1、51.9:1和76.2:1。我们的结论是,虽然异常紧密连接结构是存在于CF气道,这种功能并不是唯一的疾病,因为类似的改变发生在非CF和CF气道死后。
Previous descriptive freeze-fracture studies have suggested that the airway epithelium in cystic fibrosis (CF) is associated with proliferation and basal extension of tight junctional elements. The significance of these reports in CF has been difficult to evaluate because tight junctions are labile structures, capable of alteration, postmortem. The aim of the present study was to test the hypothesis that the abnormalities in tight junction structure reported previously are unique to CF airways, and to determine the confounding effects of postmortem autolysis. To this end, we analyzed human airway epithelial tight junctions in: (1) histologically normal tissue taken from lungs resected for pulmonary tumor (i.e., resection controls), (2) lungs from patients who died of nonrespiratory causes (i.e., postmortem controls), (3) lungs removed from CF patients undergoing transplantation, and (4) lungs from CF patients postmortem. Tight-junctional depth, strand number, and junctional complexity were analyzed. Basal extensions and isolated foci of tight-junctional elements were found in all groups except for the resection controls. The following two parameters were therefore assessed: (1) the number of times a junction extended below the maximal depth found in the resection controls and (2) the extent of junctional elements that were isolated and distant from the apico-lateral junctional belt. The mean frequencies of occurrence of junctional extension beyond the normal maximum were 4.8% for the CF transplant, 23.6% for the control postmortem, and 48.8% for the CF postmortem group. The ratios of the lengths of the strands making up the isolated foci to the lengths of the apical tight junction belt were 4.6:1, 51.9:1, and 76.2:1 for the CF transplant, control postmortem, and CF postmortem groups, respectively. We conclude that although abnormal tight-junctional structure is present in CF airways, this feature is not unique to the disease as similar alterations occur in both non-CF and CF airways postmortem.