Sharma R, Schumacher U
University of Southampton, Human Morphology School of Medicine, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16 7PX, UK.
Adv Anat Embryol Cell Biol. 2001;160:III-IX, 1-91. doi: 10.1007/978-3-642-56704-9.
The understanding of mechanisms responsible for alterations in mucin synthesis and secretions is essential in elucidating the aetiology of intestinal disorders. The existence of distinct mucins and M-cell transport mechanisms, and their beneficial effects, have long been recognised. Since nutritional and bacterial factors alter the mucin characteristics and are relevant to planning preventative strategies for intestinal diseases, the studies described in this monograph were designed to test the hypothesis that mucin composition and endocrine status of the intestinal tract are altered by dietary constituents and microbial flora. A study of gut-associated lymphoid tissue (GALT) was undertaken to test the hypothesis that lymphocyte-epithelial interactions influence the glycosylation of cells overlying Peyer's patches. The effects of diet and microbial flora were analysed by comparing the data from male Wistar germ-free rats, with conventional or human flora. Such rats were fed either a commercial diet, containing crude fibre, or a purified diet. Bone marrow transfers from syngeneic Balb/c mice to severe combined immunodeficient (SCID) mice were made to induce the formation of GALT. A comparison was made of the glycoconjugate profile of Peyer's patches in the guts of mice and humans. The results of the study showed that feeding a fibre-rich diet to germ-free rats resulted in increased villus-crypt lengths, decreased carboxylated mucin content of goblet cells, increased N-acetylglucosamine and sialic acid residues in the surface goblet cells, and a reduction in the number of endocrine cells in the small intestine. The lectin markers revealed M-cell development in the dome epithelium of the reconstituted SCID mice. Mouse M cells were labelled by fucose-specific lectins but in human Peyer's patches no distinct M-cell-staining pattern was observed.
(1) the interactions between diet and flora alter the mucosal architecture and the activity of endocrine cells; (2) the dietary changes are influential in modifying the epithelial mucin predominantly in the small intestine while the microbial flora influences the mucosal architecture predominantly in the large intestine; (3) the use of bone marrow transplantation from syngeneic mice into SCID mice along with lectin markers for M cells can be used to study the histogenesis of Peyer's patches; (4) the distinct differences between mouse and human Peyer's patches suggest that when considering cell surface glycoconjugates as target molecules appropriate lectin should be used for each species. A future challenge in intestinal epithelial cell biology is identifying the nature and distribution of cell surface receptors for specific dietary components and bacteria.
了解粘蛋白合成和分泌改变的机制对于阐明肠道疾病的病因至关重要。不同粘蛋白和M细胞转运机制的存在及其有益作用早已得到认可。由于营养和细菌因素会改变粘蛋白特性,且与肠道疾病预防策略的制定相关,因此本专著中描述的研究旨在检验以下假设:饮食成分和微生物菌群会改变肠道的粘蛋白组成和内分泌状态。开展了一项关于肠道相关淋巴组织(GALT)的研究,以检验淋巴细胞与上皮细胞的相互作用会影响派尔集合淋巴结上方细胞糖基化的假设。通过比较雄性Wistar无菌大鼠与常规或人类菌群大鼠的数据,分析饮食和微生物菌群的影响。这些大鼠分别喂食含粗纤维的商业饲料或纯化饲料。将同基因Balb/c小鼠的骨髓移植到严重联合免疫缺陷(SCID)小鼠体内,以诱导GALT形成。对小鼠和人类肠道中派尔集合淋巴结的糖缀合物谱进行了比较。研究结果表明,给无菌大鼠喂食富含纤维的饮食会导致绒毛 - 隐窝长度增加、杯状细胞羧化粘蛋白含量降低、表面杯状细胞中N - 乙酰葡糖胺和唾液酸残基增加,以及小肠内分泌细胞数量减少。凝集素标记显示重组SCID小鼠穹窿上皮中有M细胞发育。小鼠M细胞被岩藻糖特异性凝集素标记,但在人类派尔集合淋巴结中未观察到明显的M细胞染色模式。
(1)饮食与菌群之间的相互作用会改变黏膜结构和内分泌细胞的活性;(2)饮食变化主要影响小肠上皮粘蛋白的修饰,而微生物菌群主要影响大肠的黏膜结构;(3)将同基因小鼠的骨髓移植到SCID小鼠体内并结合M细胞的凝集素标记可用于研究派尔集合淋巴结的组织发生;(4)小鼠和人类派尔集合淋巴结之间的明显差异表明,在将细胞表面糖缀合物视为靶分子时,应为每个物种使用合适的凝集素。肠道上皮细胞生物学未来的一个挑战是确定特定饮食成分和细菌的细胞表面受体的性质和分布。