Uesu T, Mizuno M, Inoue H, Tomoda J, Tsuji T
First Department of Internal Medicine, Okayama University Medical School, Japan.
Lab Invest. 1995 May;72(5):587-91.
The complement system is thought to be one of the factors involved in damaging the colonic mucosa in the pathogenesis of ulcerative colitis (UC). Several membrane-bound factors that regulate complement activation have been identified.
To elucidate alteration(s) of the complement regulatory proteins and to add to the understanding of the role of the complement-related immune responses in the pathogenesis of UC, we immunohistochemically examined the distribution of decay accelerating factor (DAF), CD59/homologous restriction factor 20 (HRF20), and membrane cofactor protein (MCP) in colonic mucosa with UC and compared it with that in normal and inflammatory control mucosae.
In normal colonic epithelia, the cell surface distribution of DAF and CD59/HRF20 was confined to the apical domain, whereas MCP was present on the basolateral surface. Although MCP expression in active UC was not significantly different from normal mucosa, DAF and CD59/HRF20 expression on epithelial cells of UC was markedly enhanced in relation to the severity of mucosal inflammation. In the colonic epithelia of active UC, DAF and CD59/HRF20 were not only overexpressed on the apical surface but also were distributed to the basolateral membrane. The altered cell surface distribution of these molecules was also confirmed by immunoelectron microscopy. The enhanced expression of DAF and CD59/HRF20 was not specific to UC but was observed in colonic mucosa of inflammatory controls, such as ischemic colitis.
Our results indicate that altered regulation of complement activation is present in UC mucosa, but whether it may play a causal role in the immunologic disorders leading to UC remains to be elucidated.
补体系统被认为是溃疡性结肠炎（UC）发病机制中损伤结肠黏膜的因素之一。已鉴定出几种调节补体激活的膜结合因子。
为了阐明补体调节蛋白的改变，并增进对补体相关免疫反应在UC发病机制中作用的理解，我们采用免疫组织化学方法检测了UC结肠黏膜中衰变加速因子（DAF）、CD59/同源限制因子20（HRF20）和膜辅助蛋白（MCP）的分布，并将其与正常及炎症对照黏膜中的分布进行比较。
在正常结肠上皮中，DAF和CD59/HRF20的细胞表面分布局限于顶端区域，而MCP存在于基底外侧表面。虽然活动期UC中MCP的表达与正常黏膜无显著差异，但UC上皮细胞上DAF和CD59/HRF20的表达随黏膜炎症严重程度显著增强。在活动期UC的结肠上皮中，DAF和CD59/HRF20不仅在顶端表面过度表达，而且还分布于基底外侧膜。免疫电子显微镜也证实了这些分子细胞表面分布的改变。DAF和CD59/HRF20表达的增强并非UC所特有，在炎症对照如缺血性结肠炎的结肠黏膜中也观察到。
我们的结果表明，UC黏膜中存在补体激活调节的改变，但它是否在导致UC的免疫紊乱中起因果作用仍有待阐明。
