title: Neutrophil deactivation by influenza A virus. Role of hemagglutinin binding to specific sialic acid-bearing cellular proteins.
abstract: Bacterial superinfections are the most common cause of mortality during influenza epidemics. Depression of phagocyte functions by influenza A viruses (IAVs) is a likely contributory cause of such infections. We used an in vitro model of viral depression of neutrophil respiratory burst responses to FMLP and PMA to examine the mechanism of IAV-induced phagocyte deactivation. Respiratory burst responses or intracellular calcium mobilization were triggered by the virus itself, but these were not causally related to deactivation. By treating neutrophils with neuraminidase, and by use of purified IAV hemagglutinin (HA) preparations, cross-linking of sialic acid-bearing neutrophil surface components by the IAV HA was shown to be responsible for deactivation. IAV competed for binding to neutrophils with Abs directed against CD43, sialyl-Le(x), CD45, and gangliosides. Deactivation could be reproduced by treating neutrophils with anti-CD43 or -sialyl-Le(x) Abs in the absence of IAV. However, treatment of neutrophils with elastase markedly reduced CD43 expression, without affecting overall IAV binding or the ability of IAV to cause deactivation. Hence, although IAV binding to CD43 can account for deactivation, other IAV-binding proteins exist (e.g., those bearing sialyl-Le(x)) that can independently mediate functional depression.
authors.affiliation: Boston University School of Medicine, Department of Medicine, Boston 02118, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: L S
authors.initials: LS
authors.lastname: Liou
authors.forename: M R
authors.initials: MR
authors.lastname: White
authors.forename: M M
authors.initials: MM
authors.lastname: Kazhdan
authors.forename: J L
authors.initials: JL
authors.lastname: Tauber
authors.forename: A I
authors.initials: AI
authors.lastname: Tauber
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006389:Hemagglutinins, Viral / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology*; D019272:Leukocyte Elastase; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009439:Neuraminidase / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D010196:Pancreatic Elastase / Q000494:pharmacology; D011991:Receptors, Virus / Q000378:metabolism; D012794:Sialic Acids / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D006389:Hemagglutinins, Viral; D016177:Macrophage-1 Antigen; D011991:Receptors, Virus; D012794:Sialic Acids; D003208:Concanavalin A; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006861:Hydrogen Peroxide; D009439:Neuraminidase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium