Nakamura S, Ohtani H, Watanabe Y, Fukushima K, Matsumoto T, Kitano A, Kobayashi K, Nagura H
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Lab Invest. 1993 Jul;69(1):77-85.
The cell adhesion between vascular endothelial cells and leukocytes is an important process for the immuno-inflammatory changes. To clarify the basic features of inflammatory bowel disease (IBD), studies of in situ localization of the cell adhesion molecules are required.
We analyzed the immunohistochemical localization of the adhesion molecules (ICAM-1, LFA-1, Mac-1, VCAM-1, VLA-4, P- and E-selectins) in IBD, stressing phenotypical changes of endothelial cells.
In the normal mucosa, ICAM-1 was expressed in capillaries and venules, LFA-1 in some lymphocytes and VLA-4 in most lymphocytes. VCAM-1 was expressed sporadically in venules and constantly in follicular dendritic cells (FDC) in lymphoid follicles. Both E- and P-selectins were sporadically expressed in venules. In actively inflamed mucosa in IBD, a marked increase of all these antigens was observed; ICAM-1+ inflammatory infiltrates (lymphocytes, plasma cells, and macrophages) and ICAM-1+ venules increased paralleled to the degree of inflammation. LFA-1+ and VLA-4+ mononuclear cells and Mac-1+ granulocytes increased in number. However, expression of VCAM-1 in venules or capillaries was not increased. FDC constantly expressed VCAM-1. E- and P-selectins+ venules increased in actively inflamed tissue particularly at the base of ulcers. Immunoelectron microscopy confirmed expression of these antigens along the plasma membranes (functional localization) and in rough endoplasmic reticulum or in perinuclear spaces (localization during the intracellular synthesis).
Our study suggested that increased expression of the adhesion molecules in IBD promotes the recruitment of granulocytes and lymphocytes through blood vessels and the cell interaction between lymphocytes-antigen presenting cells or among lymphocytes, thereby sustaining the immuno-inflammatory process in IBD. The present study emphasizes the importance of microenvironmental changes including the endothelial activation in the immuno-inflammatory changes.
血管内皮细胞与白细胞之间的细胞黏附是免疫炎症变化的一个重要过程。为阐明炎症性肠病（IBD）的基本特征，需要对细胞黏附分子进行原位定位研究。
我们分析了IBD中黏附分子（ICAM - 1、LFA - 1、Mac - 1、VCAM - 1、VLA - 4、P - 和E - 选择素）的免疫组织化学定位，重点关注内皮细胞的表型变化。
在正常黏膜中，ICAM - 1在毛细血管和小静脉中表达，LFA - 1在一些淋巴细胞中表达，VLA - 4在大多数淋巴细胞中表达。VCAM - 1在小静脉中偶尔表达，在淋巴滤泡的滤泡树突状细胞（FDC）中持续表达。E - 和P - 选择素在小静脉中均偶尔表达。在IBD的活动性炎症黏膜中，所有这些抗原均显著增加；ICAM - 1 + 炎症浸润（淋巴细胞、浆细胞和巨噬细胞）以及ICAM - 1 + 小静脉与炎症程度平行增加。LFA - 1 + 和VLA - 4 + 单核细胞以及Mac - 1 + 粒细胞数量增加。然而，小静脉或毛细血管中VCAM - 1的表达并未增加。FDC持续表达VCAM - 1。E - 和P - 选择素 + 小静脉在活动性炎症组织中增加，尤其是在溃疡底部。免疫电子显微镜证实这些抗原沿质膜（功能定位）以及在粗面内质网或核周间隙（细胞内合成期间的定位）表达。
我们的研究表明，IBD中黏附分子表达增加促进粒细胞和淋巴细胞通过血管募集以及淋巴细胞 - 抗原呈递细胞之间或淋巴细胞之间的细胞相互作用，从而维持IBD中的免疫炎症过程。本研究强调了包括内皮细胞活化在内的微环境变化在免疫炎症变化中的重要性。
