Influenza-Induced Priming and Leak of XXXX Lung Microvascular Endothelium upon Exposure to @entity794 .

@entity1 @entity778 @entity61320 @entity19 @entity649 @entity4 @entity794 @entity651 @entity683 @entity1576 @entity6124 @entity204 @entity10736
UNASSIGNED: A major cause of @entity204 after @entity683 virus infection is @entity651 due to a bacterial superinfection, yet the mechanism is unknown. @entity204 has been attributed to virus-induced immunosuppression and @entity6124 , but this hypothesis is based on data from the preantibiotic era and animal models that omit antimicrobial therapy. Because of diagnostic uncertainty, most @entity1 with @entity683 receive antibiotics, making @entity6124 unlikely. @entity1576 after superinfection presents as acute @entity649 , a disorder characterized by lung microvascular leak and @entity4 . The objective of this study was to determine whether the @entity683 virus sensitizes the lung endothelium to leak upon exposure to circulating bacterial-derived molecular patterns from @entity794 . In vitro as well as in vivo models of @entity683 followed by @entity794 superinfection were used. Molecular mechanisms were explored using molecular biology, knockout @entity19 , and @entity1 autopsy specimens. @entity778 sensitized @entity1 lung endothelium to leak when challenged with @entity794 , even at low doses of @entity683 and even when the pathogens were given days apart. Influenza virus increased endothelial expression of @entity10736 both in vitro and in intact lungs, a finding corroborated by @entity1 autopsy specimens of @entity1 with @entity683 . Leak was recapitulated with protein A, a @entity10736 ligand, and sequential infection caused protein A-dependent loss of IkB, cleavage of @entity61320 , and lung endothelial apoptosis. @entity19 infected sequentially with @entity683 virus and @entity794 developed significantly @entity4 that was protein A and @entity10736 dependent. Influenza virus primes the lung endothelium to leak, predisposing @entity1 to acute @entity649 upon exposure to @entity794 .
