Olszewska-Pazdrak B, Casola A, Saito T, Alam R, Crowe S E, Mei F, Ogra P L, Garofalo R P
Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555-0369, USA.
J Virol. 1998 Jun;72(6):4756-64. doi: 10.1128/JVI.72.6.4756-4764.1998.
Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infancy, a syndrome characterized by wheezing, respiratory distress, and the pathologic findings of peribronchial mononuclear cell infiltration and release of inflammatory mediators by basophil and eosinophil leukocytes. Composition and activation of this cellular response are thought to rely on the discrete target cell selectivity of C-C chemokines. We demonstrate that infection in vitro of human epithelial cells of the lower respiratory tract by RSV induced dose- and time-dependent increases in mRNA and protein secretion for RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha). Production of MCP-1 and MIP-1alpha was selectively localized only in epithelial cells of the small airways and lung. Exposure of epithelial cells to gamma interferon (IFN-gamma), in combination with RSV infection, induced a significant increase in RANTES production that was synergistic with respect to that obtained by RSV infection or IFN-gamma treatment alone. Epithelial cell-derived chemokines exhibited a strong chemotactic activity for normal human blood eosinophils. Furthermore, eosinophils were susceptible to RSV and released RANTES and MIP-1alpha as a result of infection. Therefore, the inflammatory process in RSV-induced bronchiolitis appears to be triggered by the infection of epithelial cells and further amplified via mechanisms driven by IFN-gamma and by the secretion of eosinophil chemokines.
呼吸道合胞病毒（RSV）是婴儿期急性细支气管炎的主要病因，该综合征的特征为喘息、呼吸窘迫，以及支气管周围单核细胞浸润和嗜碱性粒细胞及嗜酸性粒细胞释放炎症介质的病理表现。这种细胞反应的组成和激活被认为依赖于C-C趋化因子离散的靶细胞选择性。我们证明，RSV体外感染人下呼吸道上皮细胞会导致调节激活正常T细胞表达和分泌因子（RANTES）、单核细胞趋化蛋白-1（MCP-1）和巨噬细胞炎性蛋白-1α（MIP-1α）的mRNA和蛋白分泌呈剂量和时间依赖性增加。MCP-1和MIP-1α的产生仅选择性地定位于小气道和肺的上皮细胞中。上皮细胞暴露于γ干扰素（IFN-γ）并结合RSV感染，会导致RANTES产生显著增加，这相对于单独的RSV感染或IFN-γ治疗具有协同作用。上皮细胞衍生的趋化因子对正常人血嗜酸性粒细胞表现出强烈的趋化活性。此外，嗜酸性粒细胞对RSV敏感，并因感染而释放RANTES和MIP-1α。因此，RSV诱导的细支气管炎中的炎症过程似乎由上皮细胞感染触发，并通过IFN-γ驱动的机制和嗜酸性粒细胞趋化因子的分泌进一步放大。
