Singh Baljit, Tschernig Thomas, van Griensven Martijn, Fieguth Armin, Pabst Reinhard
Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Canada.
Virchows Arch. 2003 May;442(5):491-5. doi: 10.1007/s00428-003-0802-6. Epub 2003 Apr 17.
Recently, vascular adhesion protein-1 (VAP-1) was implicated in adhesion and transmigration of lymphocytes across endothelial cells in liver and other organs. There is very little information on VAP-1 expression in normal and inflamed lungs. Therefore, we conducted a study to localize VAP-1 in normal mice and human lungs and in two distinct murine models of lung inflammation. Normal mice and human lungs revealed VAP-1 expression in the endothelium of large and mid-sized pulmonary vessels but not in alveolar septae, airway epithelium or blood cells. Mice that lack the lpr(-/-) gene and develop extensive lymphocytic infiltration in their lungs showed VAP-1 expression similar to the normal mice lungs. Mice subjected to cecal ligation and puncture developed acute lung inflammation and showed VAP-1 not only in endothelial cells but also in inflammatory cells in perivascular areas at 72 h after the procedure. We concluded that VAP-1 expression may contribute to the functional heterogeneity of endothelial cells within the lung to create distinct sites for the recruitment of inflammatory cells. Furthermore, since VAP-1 is expressed over a longer period of time in inflamed lungs, it may even be a suitable target for drug delivery and therapeutic manipulations.
最近,血管粘附蛋白-1(VAP-1)被认为与淋巴细胞在肝脏及其他器官中跨内皮细胞的粘附和迁移有关。关于VAP-1在正常肺组织和炎症肺组织中的表达情况,目前所知甚少。因此,我们开展了一项研究,旨在定位VAP-1在正常小鼠和人肺组织以及两种不同的小鼠肺部炎症模型中的表达。正常小鼠和人肺组织显示,VAP-1表达于大中型肺血管的内皮细胞,而在肺泡隔、气道上皮或血细胞中未检测到。缺乏lpr(-/-)基因且肺部出现广泛淋巴细胞浸润的小鼠,其VAP-1表达与正常小鼠肺组织相似。接受盲肠结扎和穿刺的小鼠发生急性肺部炎症,在术后72小时,不仅在内皮细胞中检测到VAP-1,在血管周围区域的炎症细胞中也检测到VAP-1。我们得出结论,VAP-1的表达可能有助于肺内内皮细胞的功能异质性,从而为炎症细胞的募集创造不同的位点。此外,由于VAP-1在炎症肺组织中表达的时间更长,它甚至可能是药物递送和治疗操作的合适靶点。