Inhibitory effect of pulmonary surfactant on Sendai virus infection in rat lungs.
Intranasal infection of rats with active (infectious) Sendai virus enhances secretion of tryptase Clara, a Sendai virus-activating protease, into the bronchial lumen by Clara cells of the bronchial epitheliums, and inversely suppresses secretion of pulmonary surfactant, an inhibitor of the protease, into the lumen [Kido H et al. (1993) FEBS Lett 322: 115-119]. A trypsin-resistant mutant, TR-2, showed similar effects, although its replication was restricted to a single cycle in the lungs. In contrast, neither nonactive (noninfectious) wild-type virus possessing receptor-binding activity and lacking envelope fusion activity nor UV-inactivated virus retaining receptor binding and envelope fusion activities altered the mode of secretions. These results indicate that viral replication is required for producing a condition in the bronchial lumen for proteolytic activation of progeny virus, thereby infection is extended to a fatal pneumonia. On the other hand, intranasal administration of infected rats with pulmonary surfactant suppressed activation of progeny virus and pathological changes in the lungs, suggesting a therapeutic use of pulmonary surfactant for influenza pneumonia.
Tashiro
M
M
Department of Virology 1, National Institute of Health, Tokyo, Japan.
Beppu
Y
Y
Sakai
K
K
Kido
H
H
D000818:Animals; D002460:Cell Line; D008168:Lung / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D018108:Respirovirus / Q000187:drug effects* / Q000254:growth & development; D010253:Respirovirus Infections / Q000188:drug therapy*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D053802:Tryptases
D011663:Pulmonary Surfactants; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C075431:tryptase Clara; D053802:Tryptases