Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus.
Oxidants and neutrophils contribute to lung injury during influenza A virus (IAV) infection. Surfactant protein (SP)-D plays a pivotal role in restricting IAV replication and inflammation in the first several days after infection. Despite its potent anti-inflammatory effects in vivo, preincubation of IAV with SP-D in vitro strongly increases neutrophil respiratory burst responses to the virus. Several factors are shown to modify this apparent proinflammatory effect of SP-D. Although multimeric forms of SP-D show dose-dependent augmentation of respiratory burst responses, trimeric, single-arm forms either show no effect or inhibit these responses. Furthermore, if neutrophils are preincubated with multimeric SP-D before IAV is added, oxidant responses to the virus are significantly reduced. The ability of SP-D to increase neutrophil uptake of IAV can be dissociated from enhancement of oxidant responses. Finally, several other innate immune proteins that bind to SP-D and/or IAV (i.e., SP-A, lung glycoprotein-340 or mucin) significantly reduce the ability of SP-D to promote neutrophil oxidant response. As a result, the net effect of bronchoalveolar lavage fluids is to increase neutrophil uptake of IAV while reducing the respiratory burst response to virus.
White
Mitchell R
MR
Dept. of Medicine, Boston University School of Medicine, MA 02118, USA.
Crouch
Erika
E
Vesona
Jenny
J
Tacken
Paul J
PJ
Batenburg
Joseph J
JJ
Leth-Larsen
Rikke
R
Holmskov
Uffe
U
Hartshorn
Kevan L
KL
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016466:CHO Cells; D002642:Chick Embryo; D006224:Cricetinae; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008168:Lung / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology / Q000494:pharmacology; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology* / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology*
D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C116303:glycoprotein 340; D006861:Hydrogen Peroxide