Devalia J L, Godfrey R W, Sapsford R J, Severs N J, Jeffery P K, Davies R J
Dept of Respiratory Medicine, St. Bartholomew's Hospital, London, UK.
Eur Respir J. 1994 Nov;7(11):1958-65.
Both animal and human studies have suggested that histamine increases airway epithelial cell permeability in vivo. In order to study the effect of histamine on paracellular epithelial permeability and tight junctional integrity, we have cultured human bronchial epithelial cells to confluency and investigated the effect of topically applied 0.1-20.0 microM histamine. Cultures were established on microporous membranes of tissue culture cell inserts and used for the assessment of: 1) transepithelial movement of radiolabelled mannitol (14C-mannitol) and bovine serum albumin (14C-BSA), in the luminal to serosal direction and 2) changes in electrical resistance of the cultures. Epithelial cell cultures were also established on plastic coverslips, in order to determine tight junction morphology by freeze-fracture electron microscopy, and to assess junctional integrity by lanthanum penetration, using thin sections. Compared with untreated control cultures, 0.1-10 microM histamine did not significantly alter the movement of either 14C-mannitol or 14C-BSA across the epithelial cultures at any time during incubation, but caused an increase in the electrical resistance of the cultures, which was maximal by 6 h of incubation. The morphology of the tight junctions revealed by freeze-fracture and junctional integrity (the latter determined by the degree of lanthanum penetration) were similar in untreated control cultures and cultures incubated with histamine. These studies indicate that histamine does not have a direct effect on paracellular bronchial epithelial permeability in vitro.
动物和人体研究均表明，组胺可在体内增加气道上皮细胞的通透性。为了研究组胺对上皮细胞旁通透性和紧密连接完整性的影响，我们将人支气管上皮细胞培养至汇合状态，并研究了局部应用0.1 - 20.0微摩尔组胺的效果。在组织培养细胞插入物的微孔膜上建立培养物，并用于评估：1）放射性标记的甘露醇（14C - 甘露醇）和牛血清白蛋白（14C - BSA）从管腔到浆膜方向的跨上皮转运，以及2）培养物电阻的变化。还在塑料盖玻片上建立上皮细胞培养物，以便通过冷冻断裂电子显微镜确定紧密连接形态，并使用薄片通过镧渗透评估连接完整性。与未处理的对照培养物相比，0.1 - 10微摩尔组胺在孵育期间的任何时间都不会显著改变14C - 甘露醇或14C - BSA跨上皮培养物的转运，但会导致培养物电阻增加，在孵育6小时时达到最大值。冷冻断裂显示的紧密连接形态和连接完整性（后者由镧渗透程度决定）在未处理的对照培养物和用组胺孵育的培养物中相似。这些研究表明，组胺在体外对支气管上皮细胞旁通透性没有直接影响。
