title: Exogenous administration of vascular endothelial growth factor prior to human respiratory syncytial virus a2 infection reduces pulmonary pathology in neonatal lambs and alters epithelial innate immune responses.
abstract: Human respiratory syncytial virus (RSV) affects thousands of children every year. Vascular endothelial growth factor (VEGF) is a regulator of vasculogenesis, pulmonary maturation, and immunity. In order to test the extent to which VEGF may alter RSV infection, 4 groups of lambs received either human recombinant VEGF (rhVEGF) or phosphate-buffered saline (PBS) pretreatment followed by inoculation with human RSV strain A2 or sterile medium. Lambs in each group were sacrificed at 2, 4, and 6 days post infection. Expression of surfactant protein-A (SP-A), surfactant protein-D (SP-D), sheep β-defensin-1 (SBD-1), tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-8, interferon β, and endogenous VEGF were measured to determine effect of rhVEGF pretreatment. RSV lambs pretreated with rhVEGF had reduced viral mRNA and decreased pulmonary pathology at day 6. Pretreatment with rhVEGF increased mRNA expression of SP-A, SBD-1, and TNFα, with alteration of expression in RSV lambs. Endogenous VEGF mRNA levels were increased at day 2 regardless of pretreatment. Pretreatment with rhVEGF increased pulmonary cellular proliferation in RSV lambs at day 4 post infection. Overall, these results suggest that pretreatment with rhVEGF protein may have therapeutic potential to decrease RSV viral load, decrease pulmonary lesion severity, and alter both epithelial innate immune responses and epithelial cell proliferation.
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA. Aolivier@iastate.edu
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Olivier
authors.forename: Jack M
authors.initials: JM
authors.lastname: Gallup
authors.forename: Albert
authors.initials: A
authors.lastname: van Geelen
authors.forename: Mark R
authors.initials: MR
authors.lastname: Ackermann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D037222:Collectins / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D023082:Defensins / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage; D020545:Respiratory Mucosa / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D037222:Collectins; D017931:DNA Primers; D023082:Defensins; D018836:Inflammation Mediators; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A