Altman L C, Ayars G H, Baker C, Luchtel D L
Department of Medicine, University of Washington, Seattle 98195.
J Allergy Clin Immunol. 1993 Oct;92(4):527-36. doi: 10.1016/0091-6749(93)90077-s.
Allergic and nonallergic rhinitis with eosinophilia syndrome are characterized by tissue eosinophilia and nasal mucosal injury. Recently, it has been shown that the adherence of eosinophils and other leukocytes to epithelial cells is mediated by intercellular adhesion molecule-1 (ICAM-1) and related adherence-promoting glycoproteins.
In this study we examined the constitutive expression of ICAM-1 on human nasal epithelial cells (HNECs), and the effects of interferon-gamma, tumor necrosis factor-gamma eosinophil major basic protein, and eosinophil cationic protein on the regulation of ICAM-1 expression on these cells. Similar studies were performed with A549 pneumocytes as comparative epithelial cells.
Constitutive expression of ICAM-1 was significantly higher on cultured HNECs than on A549 cells, although nasal epithelial cells in tissue specimens did not demonstrate detectable levels of ICAM-1. This spontaneous expression of ICAM-1 on cultured HNECs may explain the unique susceptibility of the nasal mucosa to rhinovirus infection, because ICAM-1 is the epithelial cell receptor for most rhinoviruses. Physiologic concentrations of major basic protein and eosinophil cationic protein stimulated significant upregulation of ICAM-1 on HNECs, which was comparable to that produced by interferon-gamma and tumor necrosis factor-alpha. In contrast, these eosinophil constituents did not stimulate ICAM-1 upregulation on A549 alveolar epithelial cells, although A549 cells did respond to interferon-gamma and tumor necrosis factor-alpha.
The observation that eosinophil products upregulate ICAM-1 on HNECs suggests a positive feedback mechanism, in which the products released from migrating eosinophils might promote additional HNEC-leukocyte adherence by enhancing interactions between leukocyte beta 2 integrins (CD11/18) and nasal epithelial ICAM-1.
伴有嗜酸性粒细胞增多综合征的变应性和非变应性鼻炎的特征为组织嗜酸性粒细胞增多和鼻黏膜损伤。最近研究表明，嗜酸性粒细胞和其他白细胞与上皮细胞的黏附是由细胞间黏附分子-1（ICAM-1）及相关促黏附糖蛋白介导的。
在本研究中，我们检测了人鼻上皮细胞（HNECs）上ICAM-1的组成性表达，以及干扰素-γ、肿瘤坏死因子-γ、嗜酸性粒细胞主要碱性蛋白和嗜酸性粒细胞阳离子蛋白对这些细胞上ICAM-1表达调控的影响。以A549肺细胞作为对照上皮细胞进行了类似研究。
尽管组织标本中的鼻上皮细胞未检测到ICAM-1水平，但培养的HNECs上ICAM-1的组成性表达显著高于A549细胞。培养的HNECs上ICAM-1的这种自发表达可能解释了鼻黏膜对鼻病毒感染的独特易感性，因为ICAM-1是大多数鼻病毒的上皮细胞受体。主要碱性蛋白和嗜酸性粒细胞阳离子蛋白的生理浓度刺激HNECs上ICAM-1显著上调，这与干扰素-γ和肿瘤坏死因子-α所产生的上调相当。相比之下，尽管A549细胞对干扰素-γ和肿瘤坏死因子-α有反应，但这些嗜酸性粒细胞成分并未刺激A549肺泡上皮细胞上ICAM-1的上调。
嗜酸性粒细胞产物上调HNECs上ICAM-1这一观察结果提示了一种正反馈机制，即迁移的嗜酸性粒细胞释放产物可能通过增强白细胞β2整合素（CD11/18）与鼻上皮ICAM-1之间的相互作用，促进更多的HNEC-白细胞黏附。
