Inhibition of epithelial sodium channels by respiratory syncytial virus in vitro and in vivo.
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and children worldwide. Infection of mice with RSV decreased sodium (Na(+)) dependent alveolar fluid clearance (AFC), resulting in increased lung water content and hypoxemia. RSV infection resulted in higher levels of pyrimidines and purines in the alveolar space. Intratracheal administration of UTP or UDP also decreased AFC. The effects of RSV on AFC and oxygen saturation of Balb/c mice were reversed by intraalveolar administration of antagonists of P2Y nucleotide receptors, enzymes that enhance the breakdown of pyrimidines and systemic or intranasal administration of inhibitors of the de novo pathway of pyrimidine synthesis. RSV infection of H441 or mouse tracheal epithelial cells decreased the amiloride-sensitive Na(+) currents and pretreatment of H441 cells with A77 prevented this effect. These findings indicate that the harmful effects of RSV on lung epithelia are mediated at least in part via the production of UTP and its paracrine action on ENaC.
Song
Weifeng
W
Department of Anesthesiology and Pulmonary Injury and Repair Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Wei
Shipeng
S
Matalon
Sadis
S
D000818:Animals; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity* / Q000502:physiology
D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels