Smithson J E, Campbell A, Andrews J M, Milton J D, Pigott R, Jewell D P
Gastroenterology Unit, Radcliffe Infirmary, Oxford.
Gut. 1997 Feb;40(2):234-40. doi: 10.1136/gut.40.2.234.
BACKGROUND/AIMS: Regional differences in the biology of the colonic epithelium may determine the extent of involvement by ulcerative colitis. Novel monoclonal antibodies (MAbs) were used in this study to investigate regional heterogeneity in the colonic mucosa.
MAbs generated using a method of tolerisation against common antigens in the proximal colon and distal colon were used for immunoperoxidase staining, comparative histochemistry, immunoblotting, and slot-blot analysis.
The colon specific MAbs 5F1 (IgG3) and 6G4 (IgM) stained goblet cell contents throughout the normal distal colon but staining was markedly reduced in the proximal colon (p < 0.0001). In the distal colon of patients with ulcerative colitis, whether quiescent or actively inflamed, reactivity was reduced compared with controls (p < 0.05, p < 0.001 respectively). By contrast, an overall increase in staining was seen in the uninflamed proximal colon in ulcerative colitis compared with controls (p < 0.02). Comparative staining with high iron diamine and biochemical analyses indicated that MAb 6G4 was reactive with mucin bearing sulphate or O-acetylated sialic acid groups, or both.
Regional differences in the staining characteristics of normal colonic mucin have been shown using novel monoclonal antibodies. The pattern of mucin expression throughout the colon in ulcerative colitis is altered even in the absence of histological changes.
背景/目的:结肠上皮生物学的区域差异可能决定溃疡性结肠炎的累及范围。本研究使用新型单克隆抗体(MAb)来研究结肠黏膜的区域异质性。
使用针对近端结肠和远端结肠常见抗原的耐受化方法产生的单克隆抗体用于免疫过氧化物酶染色、比较组织化学、免疫印迹和狭缝印迹分析。
结肠特异性单克隆抗体5F1(IgG3)和6G4(IgM)在整个正常远端结肠中对杯状细胞内容物进行染色,但在近端结肠中染色明显减少(p < 0.0001)。在溃疡性结肠炎患者的远端结肠中,无论处于静止期还是活动期炎症,与对照组相比反应性均降低(分别为p < 0.05,p < 0.001)。相比之下,与对照组相比,溃疡性结肠炎未发炎的近端结肠染色总体增加(p < 0.02)。高铁二胺的比较染色和生化分析表明,单克隆抗体6G4与带有硫酸盐或O-乙酰化唾液酸基团或两者的粘蛋白反应。
使用新型单克隆抗体已显示正常结肠粘蛋白染色特征的区域差异。即使在没有组织学变化的情况下,溃疡性结肠炎整个结肠的粘蛋白表达模式也会改变。