Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: Impact of chemokines and adhesion molecules
Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: Impact of chemokines and adhesion molecules
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DOI：
10.4049/jimmunol.177.3.1817
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Lohmeyer, Juergen
中科院分区：
文献类型：
--
作者：
Herold, Susanne;von Wulffen, Werner;Lohmeyer, Juergen
甲型流感病毒肺炎的特点是严重的肺损伤和高死亡率。早期感染引起单核细胞从外周血穿过内/上皮屏障进入肺泡气隙的强烈募集。然而，目前尚不清楚感染的常驻肺细胞群，肺泡上皮细胞或肺泡巨噬细胞，在甲型流感病毒感染期间引起单核细胞募集。在目前的研究中，我们调查是否甲型流感病毒感染的原代肺泡上皮细胞和常驻肺泡巨噬细胞将引起一个基底到顶端的单核细胞跨上皮迁移在体外。我们发现，感染肺泡上皮细胞与小鼠适应的流感病毒株PR/8强烈诱导释放单核细胞趋化因子CCL 2和CCL 5，然后由一个强大的单核细胞跨上皮迁移，这种单核细胞反应是严格依赖于单核细胞CCR 2，但不CCR 5趋化因子受体的表达。粘附分子途径的分析表明，ICAM-1，VCAM-1，整合素相关蛋白（CD 47），和上皮细胞表面上的连接粘附分子-C与单核细胞相互作用的作用0，和132整合素和整合素相关蛋白在单核细胞迁移过程中。重要的是，加入甲型流感病毒感染的肺泡巨噬细胞进一步增强了单核细胞以TNF-α依赖性方式穿过病毒感染的上皮细胞。总的来说，这些数据显示了病毒感染的肺泡上皮细胞在流感感染期间调节CCL 2/CCR 2依赖性单核细胞跨上皮迁移中的积极作用，这基本上依赖于经典的β（1）和β（2）整合素，但也依赖于连接粘附分子途径。
Influenza A virus pneumonia is characterized by severe lung injury and high mortality. Early infection elicits a strong recruitment of monocytes from the peripheral blood across the endo-/epithelial barrier into the alveolar air space. However, it is currently unclear which of the infected resident lung cell populations, alveolar epithelial cells or alveolar macrophages, elicit monocyte recruitment during influenza A virus infection. In the current study, we investigated whether influenza A virus infection of primary alveolar epithelial cells and resident alveolar macrophages would elicit a basal-to-apical monocyte transepithelial migration in vitro. We found that infection of alveolar epithelial cells with the mouse-adapted influenza A virus strain PR/8 strongly induced the release of monocyte chemoattractants CCL2 and CCL5 followed by a strong monocyte transepithelial migration, and this monocytic response was strictly dependent on monocyte CCR2 but not CCR5 chemokine receptor expression. Analysis of the adhesion molecule pathways demonstrated a role of ICAM-1, VCAM-I, integrin-associated protein (CD47), and junctional adhesion molecule-c on the epithelial cell surface interacting with monocyte 0, and 132 integrins and integrin-associated protein in the monocyte transmigration process. Importantly, addition of influenza A virus-infected alveolar macrophages further enhanced monocyte transmigration across virus-infected epithelium in a TNF-alpha-dependent manner. Collectively, the data show an active role for virus-infected alveolar epithelium in the regulation of CCL2/CCR2-dependent monocyte transepithelial migration during influenza infection that is essentially dependent on both classical beta(1) and beta(2) integrins but also junctional adhesion molecule pathways.