Becker S, Reed W, Henderson F W, Noah T L
Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Am J Physiol. 1997 Mar;272(3 Pt 1):L512-20. doi: 10.1152/ajplung.1997.272.3.L512.
Infection of airway epithelial cells with respiratory syncytial virus (RSV) results in the production of a restricted number of cytokines, which may modulate the inflammatory response to infection. To get a better understanding of epithelial cell-mediated inflammatory processes in RSV disease, the aim of the present study was to identify the production of mononuclear cell/eosinophil/mast cell inflammatory chemokines [monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protein-1beta, and RANTES] during productive RSV infection in airway epithelial cells. Normal human primary bronchial epithelial cell cultures, nasal epithelial cell explants, and the BEAS-2B airway epithelial cell line were inoculated with RSV, and chemokine induction was assessed during the phase of logarithmic increase in infectious virus production. Only RANTES was found to increase in epithelial cell cultures in an infection-dependent manner. Furthermore, RANTES was released only by RSV-producing cells. To determine whether RANTES was induced by RSV infection in vivo, RANTES was measured in nasal lavage fluids (NLF) from children with RSV-positive and RSV-negative upper respiratory infection and children when they were well. RANTES was increased significantly during RSV infection (128 +/- 38 pg/ml NFL) compared with non-RSV infection (42 +/- 12 pg/ml NFL) and with asymptomatic baseline (13 +/- 4 ng/ml NFL) in the same children. Because RANTES is an effective eosinophil and memory T cell chemoattractant and activator and because eosinophil-dominated inflammation is a hallmark of asthmatic airways, RANTES may play a role in the pathogenesis of RSV-induced exacerbations of airway reactivity and wheezing.
呼吸道合胞病毒（RSV）感染气道上皮细胞会导致产生数量有限的细胞因子，这些细胞因子可能调节对感染的炎症反应。为了更好地理解RSV疾病中上皮细胞介导的炎症过程，本研究的目的是确定在气道上皮细胞进行性RSV感染期间单核细胞/嗜酸性粒细胞/肥大细胞炎症趋化因子[单核细胞趋化蛋白（MCP）-1、MCP-3、巨噬细胞炎症蛋白-1β和调节激活正常T细胞表达和分泌的因子（RANTES）]的产生情况。将正常人类原代支气管上皮细胞培养物、鼻上皮细胞外植体和BEAS-2B气道上皮细胞系接种RSV，并在感染性病毒产量呈对数增加阶段评估趋化因子的诱导情况。仅发现RANTES以上皮细胞培养物中感染依赖性方式增加。此外，RANTES仅由产生RSV的细胞释放。为了确定RANTES是否在体内由RSV感染诱导，在RSV阳性和RSV阴性上呼吸道感染儿童以及健康儿童的鼻腔灌洗液（NLF）中测量RANTES。与同一儿童的非RSV感染（42±12 pg/ml NFL）和无症状基线（13±4 ng/ml NFL）相比，RSV感染期间RANTES显著增加（128±38 pg/ml NFL）。由于RANTES是一种有效的嗜酸性粒细胞和记忆T细胞趋化因子及激活剂，且嗜酸性粒细胞为主的炎症是哮喘气道的一个标志，因此RANTES可能在RSV诱导的气道反应性加重和喘息的发病机制中起作用。
