Fehrenbach H, Kasper M, Tschernig T, Shearman M S, Schuh D, Müller M
Institute of Pathology, University Clinics Carl Gustav Carus, Technical University of Dresden, Germany.
Cell Mol Biol (Noisy-le-grand). 1998 Nov;44(7):1147-57.
The transmembrane receptor (RAGE) of advanced glycation endproducts (AGEs), is abundantly present in the lung. Although the interaction of AGEs and RAGE plays an important role in vasculopathies, particularly in diabetes, the lung is not a classical target organ of diabetes. Thus, the role of RAGE in the lung is still obscure. This study sought to precisely localise RAGE in the lungs of rat and human by immunohistochemistry, double immunofluorescence and immunoelectron microscopy using a polyclonal antiserum developed against human recombinant RAGE. Anti-RAGE immunoreactivity was prominent in alveolar epithelial type I pneumocytes, while it was absent from type II pneumocytes and capillary endothelium. Cell type specificity was demonstrated by colocalisation with well established cell markers. Quantitative immunoelectron microscopy of cryo-substituted, Lowicryl-embedded rat and human specimens demonstrated a unique labelling pattern of RAGE in that it selectively localised to the basal cell membrane of type I pneumocytes. Labelling pattern was independent of the mode of fixation. Equivalent labelling densities were calculated from a fibrotic rat lung 3 months after irradiation. This highly selective localisation of RAGE to the basal face of type I pneumocytes and its absence from capillary endothelium might explain the resistance of the lung to typical diabetic complications.
晚期糖基化终末产物（AGEs）的跨膜受体（RAGE）在肺中大量存在。尽管AGEs与RAGE的相互作用在血管病变尤其是糖尿病中起重要作用，但肺并非糖尿病的典型靶器官。因此，RAGE在肺中的作用仍不清楚。本研究旨在通过免疫组织化学、双重免疫荧光和免疫电子显微镜技术，使用针对人重组RAGE制备的多克隆抗血清，精确地在大鼠和人的肺中定位RAGE。抗RAGE免疫反应在I型肺泡上皮细胞中很突出，而在II型肺泡上皮细胞和毛细血管内皮细胞中则不存在。通过与成熟的细胞标志物共定位证明了细胞类型特异性。对经冷冻置换、Lowicryl包埋的大鼠和人标本进行的定量免疫电子显微镜研究显示，RAGE具有独特的标记模式，即它选择性地定位于I型肺泡上皮细胞的基底细胞膜。标记模式与固定方式无关。从照射后3个月的纤维化大鼠肺中计算出等效的标记密度。RAGE在I型肺泡上皮细胞基底面的这种高度选择性定位以及在毛细血管内皮细胞中的缺失，可能解释了肺对典型糖尿病并发症的抵抗力。
