Jepson M A, Clark M A, Foster N, Mason C M, Bennett M K, Simmons N L, Hirst B H
Department of Physiological Sciences, University of Newcastle upon Tyne Medical School, UK.
J Anat. 1996 Dec;189 ( Pt 3)(Pt 3):507-16.
The specialised, antigen-transporting, epithelial M cells in the follicle-associated epithelium (FAE) overlying gut-associated lymphoid tissues constitute the primary target for oral delivery of vaccines. Our studies have shown that polystyrene microspheres selectively bind to, and are efficiently transcytosed by, rabbit Peyer's patch M cells in closed intestinal loops. Binding of biodegradable poly(DL-lactide-co-glycolide) microspheres to rabbit Peyer's patch FAE is an order of magnitude lower than that of polystyrene microspheres. Although poly(DL-lactide-co-glycolide) microspheres are not selectively targeted to M cells, a high proportion of those which bind to M cells are transcytosed, supporting the potential of such microspheres as vehicles for oral vaccine delivery. Comparison of the binding of polystyrene microspheres by murine FAE revealed this to be markedly less extensive than by rabbit FAE. These data demonstrate that microsphere binding by M cells depends on the surface properties of both cells and microspheres and suggest that surface modification may enhance the efficacy of microsphere delivery vehicles. One such approach is the incorporation of molecules with inherent binding specificity for M cells. Lectin-binding studies have revealed that M cells exhibit pronounced regional and species variation in glycoconjugate expression. In murine intestine, certain lectins bind selectively to M cells either in Peyer's patches or caecum, or at both sites. Selective targeting to, and transcytosis of, lectin-conjugates by M cells in ligated segments of murine intestine have also been demonstrated. While several lectins display strong selectivity for rabbit caecal M cells, none to date have been identified with specificity for rabbit or rat Peyer's patch M cells. Knowledge of human M cells is limited and no lectin has yet been identified with specificity for these cells. However, at least one lectin exhibits binding specificity for FAE in the human ileum. In the future, knowledge of the regional patterns of M cell carbohydrate expression within a species may allow lectins to be utilised to target selectively antigenic material to the mucosal immune system at specific locations.
覆盖在肠道相关淋巴组织上的滤泡相关上皮（FAE）中的特化、抗原转运上皮M细胞是口服疫苗递送的主要靶点。我们的研究表明，聚苯乙烯微球能选择性地结合兔派尔集合淋巴结M细胞，并在封闭肠袢中被高效转胞吞。可生物降解的聚（DL-丙交酯-共-乙交酯）微球与兔派尔集合淋巴结FAE的结合力比聚苯乙烯微球低一个数量级。尽管聚（DL-丙交酯-共-乙交酯）微球并非选择性地靶向M细胞，但与M细胞结合的微球中有很大比例会被转胞吞，这支持了此类微球作为口服疫苗递送载体的潜力。对小鼠FAE与聚苯乙烯微球结合情况的比较显示，其结合程度明显低于兔FAE。这些数据表明，M细胞对微球的结合取决于细胞和微球的表面特性，并提示表面修饰可能会提高微球递送载体的功效。一种这样的方法是掺入对M细胞具有固有结合特异性的分子。凝集素结合研究表明，M细胞在糖缀合物表达上表现出明显的区域和物种差异。在小鼠肠道中，某些凝集素会选择性地结合派尔集合淋巴结或盲肠中的M细胞，或在这两个部位均有结合。在小鼠肠道结扎段中，也已证明M细胞对凝集素缀合物具有选择性靶向和转胞吞作用。虽然几种凝集素对兔盲肠M细胞显示出很强的选择性，但迄今为止，尚未发现对兔或大鼠派尔集合淋巴结M细胞具有特异性的凝集素。关于人类M细胞的知识有限，尚未鉴定出对这些细胞具有特异性的凝集素。然而，至少有一种凝集素对人回肠中的FAE具有结合特异性。未来，了解一个物种内M细胞碳水化合物表达的区域模式，可能会使凝集素被用于在特定位置将抗原性物质选择性地靶向黏膜免疫系统。
