Histamine alters E-cadherin cell adhesion to increase human airway epithelial permeability
Histamine alters E-cadherin cell adhesion to increase human airway epithelial permeability
复制标题
DOI：
10.1152/japplphysiol.01134.2002
复制
发表时间：
2003-07-01
影响因子：
3.3
通讯作者：
Shasby, M
中科院分区：
文献类型：
--
作者：
Zabner, J;Winter, M;Shasby, M
在吸入过敏原的即时反应中，气道上皮的细胞旁通透性增加。组胺是吸入过敏原立即反应时释放的重要激动剂。我们假设组胺会增加人气道上皮细胞旁通透性，并通过中断e -钙粘蛋白为基础的细胞粘附来实现。组胺作用于基底外侧表面，增加了培养的人气道上皮细胞旁通透性，组胺的这种作用被组胺受体拮抗剂异丙嗪阻断。ECV304细胞表达组胺受体、N-cadherin和紧密连接元件，包括cludin，但它们不表达E-cadherin。组胺增加了转染载体并表达E-cadherin的ECV304细胞的细胞旁通透性，而在同一载体中表达lac-Z的ECV304细胞则没有增加。L细胞不表达组胺受体、钙粘蛋白或cladin。组胺降低表达人组胺受体和e -钙粘蛋白的L细胞与e -钙粘蛋白- Fc融合蛋白的粘附。组胺不改变表达组胺受体或单独表达e -钙粘蛋白的L细胞与e -钙粘蛋白融合蛋白的粘附。当应用于气道上皮细胞的顶表面时，腺病毒很难感染气道上皮细胞，因为它的受体CAR仅限于细胞的基底外侧表面。当组胺作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大约1倍。组胺的这种作用也被异丙嗪阻断。组胺通过阻断e -钙粘蛋白粘附，增加气道细胞旁通透性和气道上皮细胞对腺病毒感染的易感性。
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.