title: Neutrophil deactivation by influenza A viruses: mechanisms of protection after viral opsonization with collectins and hemagglutination-inhibiting antibodies.
abstract: Bacterial superinfections are a major cause of morbidity and mortality during influenza A virus (IAV) epidemics. Depression of phagocyte functions resulting from attachment of the IAV hemagglutinin (HA) to cell surface sialo-glycoproteins is a likely contributory cause of these infections. We have proposed that the group of collagenous lectins (termed collectins) present in blood and pulmonary surfactant play a role in initial host defense against IAV. We used here several recombinant human surfactant protein D (RhSP-D) preparations to determine the mechanism through which opsonization of IAV with collectins protects neutrophils against the deactivating effects of IAV on cellular respiratory burst responses in vitro. RhSP-D was markedly more potent than antibodies that inhibited viral hemagglutination activity (anti-HA antibodies) at protecting neutrophils in this assay. Unlike the anti-HA antibodies, RhSP-D was protective at concentrations that minimally inhibited viral hemagglutination activity. Two related features of SP-D--the degree of multimerization and the ability to cause aggregation of IAV particles--were critical determinants of the ability of SP-D to protect neutrophils against deactivation. Similarly SP-D-induced viral aggregate formation resulted in enhanced IAV binding to neutrophils and potentiated the ability of the virus itself to trigger neutrophil respiratory burst responses. In contrast to the case of IAV-antibody complexes, SP-D-IAV complexes attached to and activated neutrophils through a neuraminidase-sensitive mechanism (ie, similar to unopsonized IAV). These results indicate that collectin-mediated viral aggregation per se may be an important host defense mechanism not only by virtue of reducing the number of infectious viral particles, but also by promoting phagocyte responsiveness.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Massachusetts, 02118, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: K B
authors.initials: KB
authors.lastname: Reid
authors.forename: M R
authors.initials: MR
authors.lastname: White
authors.forename: J C
authors.initials: JC
authors.lastname: Jensenius
authors.forename: S M
authors.initials: SM
authors.lastname: Morris
authors.forename: A I
authors.initials: AI
authors.lastname: Tauber
authors.forename: E
authors.initials: E
authors.lastname: Crouch
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology*; D002352:Carrier Proteins / Q000502:physiology*; D002642:Chick Embryo; D037222:Collectins; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D006384:Hemagglutination / Q000187:drug effects*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D009895:Opsonin Proteins / Q000276:immunology*; D011487:Protein Conformation; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D016897:Respiratory Burst; D012794:Sialic Acids / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D002352:Carrier Proteins; D037222:Collectins; D006023:Glycoproteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009895:Opsonin Proteins; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011993:Recombinant Fusion Proteins; D012794:Sialic Acids; D009240:N-Formylmethionine Leucyl-Phenylalanine