In situ localization of TNFα/β, TACE and TNF receptors TNF-R1 and TNF-R2 in control and LPS-treated lung tissue
In situ localization of TNFα/β, TACE and TNF receptors TNF-R1 and TNF-R2 in control and LPS-treated lung tissue
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DOI：
10.1016/s1043-4666(03)00117-0
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发表时间：
2003-05-01
期刊：
影响因子：
3.8
通讯作者：
Ermert, L
中科院分区：
文献类型：
--
作者：
Ermert, M;Pantazis, C;Ermert, L
肿瘤坏死因子（TNF）与几种感染性和炎症性肺部疾病有关。两种密切相关的变异，TNFalpha和TNFbeta，通过两种不同的TNF受体，55-kDa TNF- r1和75-kDa TNF- r2，引发各种细胞反应。最近，研究人员描述了一种TNFalpha转化酶（TACE），它可以切割并释放膜结合的TNFalpha。本研究采用免疫组化技术研究了正常大鼠和人肺组织中TNFalpha/ β、TACE和TNF-R1/R2的组成性表达。此外，原位杂交法定位tnffalpha和TNFbeta mRNA。在不同类型的肺细胞中均检测到tnf - α和tnf - β。TNFalpha在支气管上皮细胞和血管平滑肌细胞中的表达尤其突出，其次是肺泡巨噬细胞。TNFalpha信息的原位杂交和TACE免疫染色都符合这种表达谱。tnf -迄今为止只知道由淋巴细胞产生-在肺泡巨噬细胞、支气管上皮细胞、血管平滑肌细胞和内皮细胞中被证实在蛋白质和信息水平上存在。两种TNF受体均被检测到，其中TNF- r1在支气管上皮细胞和内皮细胞上表现突出。以及几乎所有细胞类型都表达TNF-R2。LPS刺激离体大鼠肺后，由于储存的TNFalpha/beta被释放，TNFalpha/beta信号强度大大降低，而TACE免疫反应性保持不变或增强，表明TNF生成增加。我们得出结论，tnf - falpha和tnf - β在人和大鼠肺中由几种非白细胞细胞类型组成性表达。与TACE和TNF受体R1和R2的表达相一致，这一发现表明，除了已知的TNF系统在成人肺不同腔室的炎症生理功能中的作用外，除了白细胞/巨噬细胞群外，血管系统和支气管组织也受到特别关注。2003爱思唯尔科学有限公司版权所有。
Tumor necrosis factor (TNF) has been implicated in several infectious and inflammatory lung diseases. Two closely related,variants, TNFalpha and TNFbeta, elicit various cellular responses via two distinct TNF receptors, the 55-kDa TNF-R1 and the 75-kDa TNF-R2. Recently, a TNFalpha-converting enzyme (TACE) was described, which cleaves and releases the membrane-bound TNFalpha. In the present study in normal rat and human lung tissue, the constitutive expression of TNFalpha/beta, TACE and TNF-R1/R2 was investigated by immunohistochemical techniques. In addition, TNFalpha and TNFbeta mRNA were localized by in situ hybridization. Both TNFalpha and TNFbeta were detected in various lung cell types. Expression of TNFalpha was particularly prominent in bronchial epithelial cells and vascular smooth muscle cells, next to alveolar macrophages. Both in situ hybridization for TNFalpha message and TACE inimunostaining matched this expression profile. TNFbeta-so far only known to be produced by lymphocytes-was demonstrated in alveolar macrophages, bronchial epithelial cells, vascular smooth muscle cells and endothelial cells at the protein and the messaize level. Both TNF receptors were detected, with TNF-R1 being prominent on bronchial epithelial cells and endothelial cells. and TNF-R2 being expressed by nearly all cell types. Following LPS stimulation in isolated rat lungs TNFalpha/beta signal intensity was largely reduced due to liberation of stored TNFalpha/beta, while TACE immunoreactivity remained unchanged or was enhanced, demonstrating increased TNF generation.We conclude that both TNFalpha and TNFbeta are constitutively expressed by several non-leukocytic cell types in the human and rat lung. In concert with the expression of TACE and the TNF receptors R1 and R2, this finding suggests in addition to the known role of the TNF system in inflammation physiological functions of the TNF system in different compartments of the adult lung, with the vasculature and the bronchial tissue being of particular interest in addition to the leukocyte/macrophage populations. (C) 2003 Elsevier Science Ltd. All rights reserved.