Zabner Joseph, Winter Michael, Excoffon Katherine J D Ashbourne, Stoltz David, Ries Dana, Shasby Sandra, Shasby Michael
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
J Appl Physiol (1985). 2003 Jul;95(1):394-401. doi: 10.1152/japplphysiol.01134.2002.
During the immediate response to an inhaled allergen, there is an increase in the paracellular permeability of the airway epithelium.1 Histamine is an important agonist released during the immediate response to inhaled allergen. We hypothesized that histamine would increase human airway epithelial paracellular permeability and that it would do this by interrupting E-cadherin-based cell adhesion. Histamine, applied to the basolateral surface, increased the paracellular permeability of cultured human airway epithelia, and this effect of histamine was blocked by the histamine receptor antagonist promethazine. ECV304 cells express a histamine receptor, N-cadherin, and elements of the tight junction, including claudins, but they do not express E-cadherin. Histamine increased the paracellular permeability of ECV304 cells transfected with a vector and expressing E-cadherin but not ECV304 cells expressing lac-Z in the same vector. L cells do not express the histamine receptor, cadherins, or claudins. Histamine decreased adhesion of L cells expressing the human histamine receptor and E-cadherin to an E-cadherin-Fc fusion protein. Histamine did not alter the adhesion to the E-cadherin fusion protein of L cells expressing either the histamine receptor or E-cadherin alone. When applied to the apical surface, adenovirus poorly infects airway epithelial cells because its receptor, CAR, is restricted to the basolateral surface of the cells. When histamine was applied to the basolateral surface of airway epithelial cells, infection of the cells by adenovirus increased by approximately one log. This effect of histamine was also blocked by promethazine. Histamine increases airway paracellular permeability and increases susceptibility of airway epithelial cells to infection by adenovirus by interrupting E-cadherin adhesion.
在对吸入性变应原的即时反应过程中，气道上皮细胞旁通透性增加。组胺是在对吸入性变应原的即时反应过程中释放的一种重要激动剂。我们推测，组胺会增加人气道上皮细胞旁通透性，并且它会通过中断基于E-钙黏蛋白的细胞黏附来实现这一点。将组胺应用于基底外侧表面，可增加培养的人气道上皮细胞的细胞旁通透性，组胺的这种作用被组胺受体拮抗剂异丙嗪阻断。ECV304细胞表达一种组胺受体、N-钙黏蛋白以及包括闭合蛋白在内的紧密连接成分，但它们不表达E-钙黏蛋白。组胺增加了用载体转染并表达E-钙黏蛋白的ECV304细胞的细胞旁通透性，但没有增加在同一载体中表达lac-Z的ECV304细胞的细胞旁通透性。L细胞不表达组胺受体、钙黏蛋白或闭合蛋白。组胺降低了表达人组胺受体和E-钙黏蛋白的L细胞与E-钙黏蛋白-Fc融合蛋白的黏附。组胺对单独表达组胺受体或E-钙黏蛋白的L细胞与E-钙黏蛋白融合蛋白的黏附没有影响。当应用于顶表面时，腺病毒很难感染气道上皮细胞，因为其受体柯萨奇病毒和腺病毒受体（CAR）局限于细胞的基底外侧表面。当组胺应用于气道上皮细胞的基底外侧表面时，腺病毒对细胞的感染增加了约一个对数级。组胺的这种作用也被异丙嗪阻断。组胺通过中断E-钙黏蛋白黏附增加气道细胞旁通透性并增加气道上皮细胞对腺病毒感染的易感性。
