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新型体细胞干细胞识别抗体(A3)标记的细胞在大鼠肺发育及博来霉素诱导的肺纤维化中的分布

Distribution of cells labelled by a novel somatic stem cell-recognizing antibody (A3) in pulmonary genesis and bleomycin induced pulmonary fibrosis in rats.

作者信息

Hori M, Juniantito V, Izawa T, Ichikawa C, Tanaka M, Tanaka K, Takenaka S, Kuwamura M, Yamate J

机构信息

Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Rinku-Ourai Kita 1-58, Izumisano-shi, Osaka-598 8531, Japan.

出版信息

J Comp Pathol. 2013 May;148(4):385-95. doi: 10.1016/j.jcpa.2012.09.003. Epub 2012 Oct 11.

Abstract

Stem cells play important roles in organogenesis and remodelling after tissue injury. A monoclonal antibody (A3) has been produced against rat somatic stem cells. The present study investigated the distribution of cells labelled by A3 in the lung of fetal, neonatal and adult rats, as well as in the lung of rats with bleomycin (BLM) induced pulmonary fibrosis. In developing fetal lungs, A3(+) interstitial cells were present around the bronchi/bronchioles and arterioles, while in neonatal and adult lungs, the A3 reactivity of the interstitial cells gradually disappeared and instead, vascular endothelial cells in alveolar capillaries and arterioles expressed A3. By double immunofluorescence labelling, the A3(+) interstitial cells also expressed vimentin (a mesenchymal marker) and CD34 (a marker of immature mesenchymal cells), indicating that the interstitial cells were immature mesenchymal cells concentrated in organs as precursors to cells of connective tissues. A3(+)endothelial cells were co-expressed RECA-1 (a marker of rat endothelial cells) and A3 was localized to the cell membrane and cytoplasm of these cells by immunoelectron microscopy. In BLM induced fibrotic lesions, there were many A3(+) cells, which also expressed vimentin or RECA-1 by dual immunofluorescence labelling. There were few CD34(+)/A3(+) double positive cells. No cells co-expressed A3 and α-smooth muscle actin (a marker of well-differentiated myofibroblastic cells). Although the detailed properties of cells labelled by A3 remain to be discovered, A3 would appear to be a useful marker of immature mesenchymal cells and vascular endothelial cells in developing lungs and in pulmonary fibrosis.

摘要

干细胞在器官发生和组织损伤后的重塑过程中发挥着重要作用。已经制备了一种针对大鼠体干细胞的单克隆抗体(A3)。本研究调查了A3标记的细胞在胎鼠、新生鼠和成年鼠肺组织中的分布情况,以及在博来霉素(BLM)诱导的肺纤维化大鼠肺组织中的分布情况。在发育中的胎肺中,A3(+)间质细胞存在于支气管/细支气管和小动脉周围,而在新生鼠和成年鼠肺中,间质细胞的A3反应性逐渐消失,取而代之的是肺泡毛细血管和小动脉中的血管内皮细胞表达A3。通过双重免疫荧光标记,A3(+)间质细胞还表达波形蛋白(一种间充质标志物)和CD34(未成熟间充质细胞的标志物),这表明间质细胞是集中在器官中的未成熟间充质细胞,是结缔组织细胞的前体。A3(+)内皮细胞共表达RECA-1(大鼠内皮细胞的标志物),免疫电子显微镜显示A3定位于这些细胞的细胞膜和细胞质中。在BLM诱导的纤维化病变中,有许多A3(+)细胞,通过双重免疫荧光标记也表达波形蛋白或RECA-1。CD34(+)/A3(+)双阳性细胞很少。没有细胞同时表达A3和α-平滑肌肌动蛋白(一种分化良好的肌成纤维细胞的标志物)。尽管A3标记细胞的详细特性仍有待发现,但A3似乎是发育中的肺组织和肺纤维化中未成熟间充质细胞和血管内皮细胞的有用标志物。

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