Zhang Y, Luxon B A, Casola A, Garofalo R P, Jamaluddin M, Brasier A R
Department of Medicine, The University of Texas Medical Branch, Galveston, Texas 77555-1060, USA.
J Virol. 2001 Oct;75(19):9044-58. doi: 10.1128/JVI.75.19.9044-9058.2001.
The Paramyxovirus respiratory syncytial virus (RSV) is the primary etiologic agent of serious epidemic lower respiratory tract disease in infants, immunosuppressed patients, and the elderly. Lower tract infection with RSV is characterized by a pronounced peribronchial mononuclear infiltrate, with eosinophilic and basophilic degranulation. Because RSV replication is restricted to airway epithelial cells, where RSV replication induces potent expression of chemokines, the epithelium is postulated to be a primary initiator of pulmonary inflammation in RSV infection. The spectrum of RSV-induced chemokines expressed by alveolar epithelial cells has not been fully investigated. In this report, we profile the kinetics and patterns of chemokine expression in RSV-infected lower airway epithelial cells (A549 and SAE). In A549 cells, membrane-based cDNA macroarrays and high-density oligonucleotide probe-based microarrays identified inducible expression of CC (I-309, Exodus-1, TARC, RANTES, MCP-1, MDC, and MIP-1 alpha and -1 beta), CXC (GRO-alpha, -beta, and -gamma, ENA-78, interleukin-8 [IL-8], and I-TAC), and CX(3)C (Fractalkine) chemokines. Chemokines not previously known to be expressed by RSV-infected cells were independently confirmed by multiprobe RNase protection assay, Northern blotting, and reverse transcription-PCR. High-density microarrays performed on SAE cells confirmed a similar pattern of RSV-inducible expression of CC chemokines (Exodus-1, RANTES, and MIP-1 alpha and -1 beta), CXC chemokines (I-TAC, GRO-alpha, -beta, and -gamma, and IL-8), and Fractalkine. In contrast, TARC, MCP-1, and MDC were not induced, suggesting the existence of distinct genetic responses for different types of airway-derived epithelial cells. Hierarchical clustering by agglomerative nesting and principal-component analyses were performed on A549-expressed chemokines; these analyses indicated that RSV-inducible chemokines are ordered into three related expression groups. These data profile the temporal changes in expression by RSV-infected lower airway epithelial cells of chemokines, chemotactic proteins which may be responsible for the complex cellular infiltrate in virus-induced respiratory inflammation.
副粘病毒呼吸道合胞病毒（RSV）是引起婴儿、免疫抑制患者和老年人严重流行性下呼吸道疾病的主要病原体。RSV引起的下呼吸道感染的特征是明显的支气管周围单核细胞浸润，并伴有嗜酸性粒细胞和嗜碱性粒细胞脱颗粒。由于RSV复制仅限于气道上皮细胞，而RSV复制会诱导趋化因子的有效表达，因此推测上皮细胞是RSV感染中肺部炎症的主要引发者。肺泡上皮细胞表达的RSV诱导趋化因子谱尚未得到充分研究。在本报告中，我们描绘了RSV感染的下呼吸道上皮细胞（A549和SAE）中趋化因子表达的动力学和模式。在A549细胞中，基于膜的cDNA宏阵列和基于高密度寡核苷酸探针的微阵列鉴定出CC趋化因子（I-309、Exodus-1、TARC、RANTES、MCP-1、MDC以及MIP-1α和-1β）、CXC趋化因子（GRO-α、-β和-γ、ENA-78、白细胞介素-8 [IL-8]和I-TAC）以及CX(3)C趋化因子（Fractalkine）的可诱导表达。以前未知由RSV感染细胞表达的趋化因子通过多探针核糖核酸酶保护试验、Northern印迹和逆转录PCR得到独立证实。对SAE细胞进行的高密度微阵列证实了CC趋化因子（Exodus-1、RANTES以及MIP-1α和-1β）、CXC趋化因子（I-TAC、GRO-α、-β和-γ以及IL-8）和Fractalkine的类似RSV诱导表达模式。相比之下，TARC、MCP-1和MDC未被诱导，这表明不同类型的气道来源上皮细胞存在不同的基因反应。对A549细胞表达的趋化因子进行了凝聚嵌套层次聚类和主成分分析；这些分析表明，RSV诱导的趋化因子被分为三个相关的表达组。这些数据描绘了RSV感染的下呼吸道上皮细胞中趋化因子（趋化蛋白）表达的时间变化，这些趋化因子可能是病毒诱导的呼吸道炎症中复杂细胞浸润的原因。
