Division of Drug Delivery and Tissue Engineering, School of Pharmacy, Boots Science Building, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Biochem Biophys Res Commun. 2011 Dec 2;415(4):579-85. doi: 10.1016/j.bbrc.2011.10.108. Epub 2011 Nov 2.
The barrier characteristics of polarized layers of Calu-3 and Caco-2 cell lines, as commonly used in vitro models of intestinal and airway mucosa, respectively, were investigated by assessing the translocation of model macromolecules and nanoparticles. The barrier capacity of the cell layers towards the movement of macromolecules and nanoparticulates differed considerably between the cell lines. Permeability studies revealed the existence of a notably larger solute molecular weight limit for paracellular diffusion in Caco-2 monolayers compared to Calu-3 cells. Removal of mucus in Calu-3 cells resulted in cell layers exhibiting a larger macromolecular permeability, in addition to improved nanoparticle translocation. Microscopic examination of the tight junctions, as cellular features that play a major role in preventing transepithelial movement of macromolecules, revealed that the appearance of cell-cell boundaries was notably different in the two cell lines, which could explain the differences in macromolecular permeability. The data overall showed that epithelial layers of airway Calu-3 and intestinal Caco-2 cell cultures in vitro exhibit a different level of restrictiveness and this is due to the cell morphology and the presence of mucus.
分别以常用于肠道和呼吸道黏膜模型的 Calu-3 和 Caco-2 细胞系为研究对象,评估模型大分子和纳米颗粒的转运情况,研究了极化细胞层的屏障特性。细胞层对大分子和纳米颗粒迁移的屏障能力在细胞系之间存在显著差异。渗透性研究表明,与 Calu-3 细胞相比,Caco-2 单层细胞中存在更大的溶质分子质量限制,以利于细胞旁扩散。在 Calu-3 细胞中去除黏液会导致细胞层表现出更大的大分子渗透性,同时还会改善纳米颗粒的转运。作为主要防止大分子跨上皮运动的细胞特征的紧密连接的显微镜检查表明,两种细胞系中细胞-细胞边界的外观明显不同,这可以解释大分子通透性的差异。总的来说,数据表明体外气道 Calu-3 和肠道 Caco-2 细胞培养物的上皮层表现出不同程度的限制,这是由于细胞形态和黏液的存在所致。