Carboni J M, Howe C L, West A B, Barwick K W, Mooseker M S, Morrow J S
Department of Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Am J Pathol. 1987 Dec;129(3):589-600.
The elaborate cytoskeletal matrix underlying the intestinal epithelial cell brush border (BB) is the hallmark of a mature enterocyte. As such, alterations in this structure are potentially useful as markers aiding in the recognition of subtle defects in cell maturation, such as those accompanying dysplasia and neoplasia. For exploration of this hypothesis, the BB components of human ileal and colonic enterocytes have been compared structurally and biochemically with the well-characterized avian BB, and alterations in the BB cytoskeleton in various states of dysplasia and neoplasia have been identified. Ultrastructural analysis of isolated human ileal BBs indicate that the human BB is structurally homologous to BBs isolated from chicken and other mammalian sources. Like other mammalian BBs (eg, from rat) the terminal web cytoskeleton of the human BB is less extensive than that in the avian BB. Immunochemical analysis of isolated human BBs indicates that the major proteins of the avian microvillar actin bundle, villin, fimbrin, and the 110-kd subunit of the 110K-calmodulin complex, are all present in the human BB. The terminal web protein myosin is also present. Unlike the terminal web of the avian BB, which contains a BB-specific isoform of spectrin, TW 260/240, the human BB contains the more widely distributed spectrin isoform, fodrin. In addition, the human BB contains multiple proteins immunoreactive with antibodies to protein 4.1, a spectrin/actin binding protein that is absent from the avian BB. Immunolocalization studies examining the distribution of the BB-specific microvillar protein, villin, in human colonic mucosa indicate that the localization of this protein is disrupted in certain dysplastic and neoplastic states. Thus, both the expression and/or distribution of BB-specific proteins such as villin may be useful markers for defects in the differentiation state of the enterocyte.
肠道上皮细胞刷状缘（BB）下方精细的细胞骨架基质是成熟肠细胞的标志。因此，这种结构的改变可能有助于识别细胞成熟过程中的细微缺陷，例如发育异常和肿瘤形成时伴随的缺陷。为了验证这一假设，已对人类回肠和结肠肠细胞的BB成分进行了结构和生化方面的比较，并与特征明确的禽类BB进行了对比，同时还确定了不同发育异常和肿瘤状态下BB细胞骨架的变化。对分离出的人类回肠BB进行超微结构分析表明，人类BB在结构上与从鸡和其他哺乳动物来源分离出的BB同源。与其他哺乳动物的BB（如大鼠的BB）一样，人类BB的终末网细胞骨架不如禽类BB发达。对分离出的人类BB进行免疫化学分析表明，禽类微绒毛肌动蛋白束的主要蛋白质、绒毛蛋白、丝束蛋白以及110K-钙调蛋白复合物的110-kd亚基在人类BB中均有存在。终末网蛋白肌球蛋白也存在。与禽类BB的终末网不同，禽类BB的终末网含有一种BB特异性的血影蛋白异构体TW 260/240，而人类BB含有分布更广泛的血影蛋白异构体血影素。此外，人类BB含有多种与抗蛋白4.1抗体发生免疫反应的蛋白质，蛋白4.1是一种血影蛋白/肌动蛋白结合蛋白，禽类BB中不存在这种蛋白。免疫定位研究检测了BB特异性微绒毛蛋白绒毛蛋白在人类结肠黏膜中的分布，结果表明在某些发育异常和肿瘤状态下，这种蛋白的定位会受到破坏。因此，绒毛蛋白等BB特异性蛋白的表达和/或分布可能是肠细胞分化状态缺陷的有用标志物。
