title: Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.
abstract: Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments.
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Weifeng
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Doran
authors.affiliation: Department of Pediatrics (Neonatology), School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
authors.affiliation: Department of Medicine (Pulmonary, Critical Care and Sleep), and the Pulmonary Injury and Repair Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.affiliation: Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
authors.forename: Stavros
authors.initials: S
authors.lastname: Garantziotis
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; sadis@uab.edu.
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000276:immunology / Q000821:virology; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D002713:Chlorine / Q000633:toxicity*; D006820:Hyaluronic Acid / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses
chemical_list: D000393:Air Pollutants; D018925:Chemokines; D002713:Chlorine; D006820:Hyaluronic Acid
keywords: bronchoalveolar lavage; cytokines; flexiVent; inflammatory cells; methacholine