title: RSV infection of human airway epithelial cells causes production of the beta-chemokine RANTES.
abstract: 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.
authors.affiliation: Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: S
authors.initials: S
authors.lastname: Becker
authors.forename: W
authors.initials: W
authors.lastname: Reed
authors.forename: F W
authors.initials: FW
authors.lastname: Henderson
authors.forename: T L
authors.initials: TL
authors.lastname: Noah
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000382:microbiology; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D002648:Child; D004847:Epithelial Cells; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity; D007251:Influenza, Human / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D008171:Lung Diseases / Q000503:physiopathology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D009297:Nasal Mucosa / Q000382:microbiology; D012367:RNA, Viral / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000503:physiopathology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D012367:RNA, Viral