Crestani B, Rolland C, Lardeux B, Fournier T, Bernuau D, Poüs C, Vissuzaine C, Li L, Aubier M
Institut National de la Santé et de la Recherche Médicale U408, Faculté de Médecine Xavier Bichat, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France.
J Immunol. 1998 May 1;160(9):4596-605.
Alpha1-acid glycoprotein (AGP) is a major acute phase protein in rat and human. AGP has important immunomodulatory functions that are potentially important for pulmonary inflammatory response. The liver is the main tissue for AGP synthesis in the organism, but the expression of AGP in the rat lung has not been investigated. We show that AGP mRNA was induced in the lung of dexamethasone-, turpentine-, or LPS-treated rats, whereas AGP mRNA was not detected in the lung of control rats. In the lung of animals treated intratracheally with LPS, in situ hybridization showed that AGP gene expression was restricted to cells located in the corners of the alveolus, consistent with an alveolar type II (ATII) cell localization. The inducible expression of the AGP gene was confirmed in vitro with SV40 T2 cells and rat ATII cells in primary culture: maximal expression required the presence of dexamethasone. IL-1 and the conditioned medium of alveolar macrophages acted synergistically with dexamethasone. Rat ATII cells secreted immunoreactive AGP in vitro when stimulated with dexamethasone or with a combination of dexamethasone and the conditioned medium of alveolar macrophages. In vivo, in the human lung, we detected immunoreactive AGP in hyperplastic ATII cells, whereas we did not detect AGP in the normal lung. We conclude that AGP is expressed in the lung in cases of inflammation and that ATII cells are the main source of AGP in the lung.
α1-酸性糖蛋白（AGP）是大鼠和人类体内的一种主要急性期蛋白。AGP具有重要的免疫调节功能，对肺部炎症反应可能具有重要意义。肝脏是机体中AGP合成的主要组织，但尚未对大鼠肺中AGP的表达进行研究。我们发现，在地塞米松、松节油或脂多糖处理的大鼠肺中可诱导AGP mRNA表达，而在对照大鼠肺中未检测到AGP mRNA。在经气管内注射脂多糖处理的动物肺中，原位杂交显示AGP基因表达局限于位于肺泡角落的细胞，这与II型肺泡上皮细胞（ATII）的定位一致。在体外，用SV40 T2细胞和原代培养的大鼠ATII细胞证实了AGP基因的可诱导表达：最大表达需要地塞米松的存在。白细胞介素-1和肺泡巨噬细胞的条件培养基与地塞米松协同作用。当用地塞米松或地塞米松与肺泡巨噬细胞条件培养基的组合刺激时，大鼠ATII细胞在体外分泌免疫反应性AGP。在体内，在人肺中，我们在增生的ATII细胞中检测到免疫反应性AGP，而在正常肺中未检测到AGP。我们得出结论，在炎症情况下肺中表达AGP，且ATII细胞是肺中AGP的主要来源。
