Koch Christian, da Silveira Alexandre B M, de Oliveira Enio C, Quint Karl, Neuhuber Winfried, Brehmer Axel, Jabari Samir
Waldkrankenhaus St. Marien gGmbH, Rathsberger Straße 57, 91054, Erlangen, Germany.
Human Anatomy Sector, ICBIM, Universidade Federal de Uberlândia, Minas Gerais, 38.400-902, Brazil.
Histochem Cell Biol. 2017 Aug;148(2):207-216. doi: 10.1007/s00418-017-1563-7. Epub 2017 Mar 29.
Patients suffering from chagasic megacolon must have an intact mucosal barrier as they survive this chronic disease for decades. A key structure of the mucosal barrier are epithelial cells. Vasoactive-intestinal-peptide (VIP)-positive nerve fibres are involved in influencing, e.g., epithelial cell proliferation, mucus secretion (e.g., mucin 2 and trefoil factor 3 of goblet cells) and inflammation or autoimmunity, all putative and/or known factors altered in chagasic megacolon. We analyzed qualitatively and quantitatively goblet cells, their specific markers, such as mucin 2 (MUC2) and trefoil factor 3 (TFF3) and enterocytes, the relation of VIP-immunoreactive nerve fibres to the epithelia, the distribution of gelsolin, a protein involved in chronic inflammation processes in the epithelia, and the proliferation rate of epithelial cells by combined 4',6-diamidino-2-phenylindole (DAPI) and phosphohistone-H3 (PHH3) staining. Goblet cells were the dominating epithelial cell type. They accounted for 38.4% of all epithelial cells in controls and changed to 58.9% in the megacolonic parts. In contrast to the overall expression in goblet cells of control epithelia, TFF3 was confined to goblet cells at the base of the crypts whereas MUC2 was found only in luminal goblet cells. Gelsolin-positive goblet cells were predominantly recognized within the controls. Finally, the mean value of mitosis increased from 1.5% within the controls up to 2.6% in the anal parts of the chagasic sepcimens. Taken together, increased cell proliferation, preponderance of goblet cells, differential MUC 2, and TFF 3 expression might all be factors maintaining an intact mucosal barrier within chagasic megacolon.
患有恰加斯病性巨结肠的患者必须具备完整的黏膜屏障，因为他们能在这种慢性疾病中存活数十年。黏膜屏障的一个关键结构是上皮细胞。血管活性肠肽（VIP）阳性神经纤维参与影响上皮细胞增殖、黏液分泌（如杯状细胞的黏蛋白2和三叶因子3）以及炎症或自身免疫，这些都是恰加斯病性巨结肠中假定和/或已知发生改变的因素。我们通过联合使用4',6-二脒基-2-苯基吲哚（DAPI）和磷酸组蛋白-H3（PHH3）染色，对杯状细胞及其特异性标志物（如黏蛋白2（MUC2）和三叶因子3（TFF3））、肠上皮细胞进行了定性和定量分析，研究了VIP免疫反应性神经纤维与上皮细胞的关系、凝溶胶蛋白（一种参与上皮细胞慢性炎症过程的蛋白质）的分布以及上皮细胞的增殖率。杯状细胞是主要的上皮细胞类型。在对照组中，它们占所有上皮细胞的38.4%，在巨结肠部分则变为58.9%。与对照上皮杯状细胞的整体表达情况不同，TFF3局限于隐窝底部的杯状细胞，而MUC2仅在腔面杯状细胞中发现。在对照组中，主要识别出凝溶胶蛋白阳性的杯状细胞。最后，有丝分裂的平均值从对照组的1.5%增加到恰加斯病标本肛门部分的2.6%。综上所述，细胞增殖增加、杯状细胞占优势、MUC2和TFF3表达差异可能都是维持恰加斯病性巨结肠内黏膜屏障完整的因素。
