Surfactant protein-A enhances respiratory syncytial virus clearance in vivo.
To determine the role of surfactant protein-A(SP-A) in antiviral host defense, mice lacking SP-A (SP-A-/-) were produced by targeted gene inactivation. SP-A-/- and control mice (SP-A+/+) were infected with respiratory syncytial virus (RSV) by intratracheal instillation. Pulmonary infiltration after infection was more severe in SP-A-/- than in SP-A+/+ mice and was associated with increased RSV plaque-forming units in lung homogenates. Pulmonary infiltration with polymorphonuclear leukocytes was greater in the SP-A-/- mice. Levels of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 were enhanced in lungs of SP-A-/- mice. After RSV infection, superoxide and hydrogen peroxide generation was deficient in macrophages from SP-A-/- mice, demonstrating a critical role of SP-A in oxidant production associated with RSV infection. Coadministration of RSV with exogenous SP-A reduced viral titers and inflammatory cells in the lung of SP-A-/- mice. These findings demonstrate that SP-A plays an important host defense role against RSV in vivo.
LeVine
A M
AM
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. leviaO@chmcc.org
Gwozdz
J
J
Stark
J
J
Bruno
M
M
Whitsett
J
J
Korfhagen
T
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000821:virology; D008168:Lung / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics* / Q000494:pharmacology; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000378:metabolism*; D010948:Viral Plaque Assay
D016207:Cytokines; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D017382:Reactive Oxygen Species