Friis S, Dabelsteen E, Sjöström H, Norén O, Jarnum S
Department of Medicine A, Rigshospitalet, Copenhagen, Denmark.
Gut. 1992 Nov;33(11):1487-92. doi: 10.1136/gut.33.11.1487.
The pepsin trypsin digest of the wheat prolamin gliadin (PT-gliadin) is deleterious to the small intestinal mucosa of coeliac patients. The handling of PT-gliadin by the intestinal epithelium in coeliac patients in remission and control individuals was investigated by in vivo instillation of PT-gliadin. The uptake of PT-gliadin was monitored by immunofluorescence microscopy of intestinal biopsy specimens, using affinity purified PT-gliadin antibodies. Control individuals show weak staining in the apical region of the enterocytes thereby showing an uptake of PT-gliadin. Coeliac patients have a conspicuous fluorescence in relation to the lateral membrane/intercellular space of enterocytes and intense staining intracellularly in the apical region. There is only weak staining in the enterocytes after the instillation was terminated, indicating an intracellular clearance. The study shows that normal enterocytes are able to take up PT-gliadin. The increased uptake in coeliac patients might be of importance for the pathogenesis either by direct toxicity or by presentation to immunocompetent cells. Furthermore, the results are in agreement with the suggestion of a functional alteration in the zonula occludens in the intestinal epithelium of coeliac patients.
小麦醇溶蛋白-麦醇溶蛋白的胃蛋白酶-胰蛋白酶消化产物(PT-麦醇溶蛋白)对乳糜泻患者的小肠黏膜有害。通过体内滴注PT-麦醇溶蛋白,研究了处于缓解期的乳糜泻患者和对照个体的肠上皮细胞对PT-麦醇溶蛋白的处理情况。使用亲和纯化的PT-麦醇溶蛋白抗体,通过对肠活检标本进行免疫荧光显微镜检查来监测PT-麦醇溶蛋白的摄取。对照个体在肠上皮细胞顶端区域显示弱阳性染色,从而表明摄取了PT-麦醇溶蛋白。乳糜泻患者在肠上皮细胞的侧膜/细胞间空间有明显荧光,在顶端区域细胞内有强烈染色。滴注终止后,肠上皮细胞中只有弱阳性染色,表明细胞内清除。该研究表明正常肠上皮细胞能够摄取PT-麦醇溶蛋白。乳糜泻患者摄取增加可能通过直接毒性或通过呈递给免疫活性细胞对发病机制具有重要意义。此外,结果与乳糜泻患者肠上皮紧密连接功能改变的观点一致。