title: Sheep lung segmental delivery strategy demonstrates adenovirus priming of local lung responses to bacterial LPS and the role of elafin as a response modulator.
abstract: Viral lung infections increase susceptibility to subsequent bacterial infection. We questioned whether local lung administration of recombinant adenoviral vectors in the sheep would alter the susceptibility of the lung to subsequent challenge with bacterial lipopolysaccharide (LPS). We further questioned whether local lung expression of elafin, a locally produced alarm anti-LPS/anti-bacterial molecule, would modulate the challenge response. We established that adenoviral vector treatment primed the lung for an enhanced response to bacterial LPS. Whereas this local effect appeared to be independent of the transgene used (Ad-o-elafin or Ad-GFP), Ad-o-elafin treated sheep demonstrated a more profound lymphopenia in response to local lung administration of LPS. The local influence of elafin in modulating the response to LPS was restricted to maintaining neutrophil myeloperoxidase activity, and levels of alveolar macrophage and neutrophil phagocytosis at higher levels post-LPS. Adenoviral vector-bacterial synergism exists in the ovine lung and elafin expression modulates such synergism both locally and systemically.
authors.affiliation: University of Edinburgh, Medical School, Edinburgh, Scotland, United Kingdom; The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, United Kingdom.
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Brown
authors.affiliation: The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Collie
authors.affiliation: The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, United Kingdom.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Shaw
authors.affiliation: The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, United Kingdom.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Rzechorzek
authors.affiliation: University of Edinburgh, Medical School, Edinburgh, Scotland, United Kingdom.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Sallenave
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000472:pathogenicity; D000257:Adenoviridae Infections / Q000235:genetics / Q000382:microbiology / Q000821:virology; D000818:Animals; D053492:Elafin / Q000096:biosynthesis; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors / Q000009:adverse effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000382:microbiology / Q000473:pathology* / Q000821:virology; D009504:Neutrophils / Q000187:drug effects; D012756:Sheep; D034561:Sheep, Domestic; D019076:Transgenes / Q000235:genetics
chemical_list: D053492:Elafin; D008070:Lipopolysaccharides