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Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator

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 quest...

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Autores principales: Brown, Thomas I., Collie, David S., Shaw, Darren J., Rzechorzek, Nina M., Sallenave, Jean-Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162618/
https://www.ncbi.nlm.nih.gov/pubmed/25216250
http://dx.doi.org/10.1371/journal.pone.0107590
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author Brown, Thomas I.
Collie, David S.
Shaw, Darren J.
Rzechorzek, Nina M.
Sallenave, Jean-Michel
author_facet Brown, Thomas I.
Collie, David S.
Shaw, Darren J.
Rzechorzek, Nina M.
Sallenave, Jean-Michel
author_sort Brown, Thomas I.
collection PubMed
description 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.
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spelling pubmed-41626182014-09-17 Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator Brown, Thomas I. Collie, David S. Shaw, Darren J. Rzechorzek, Nina M. Sallenave, Jean-Michel PLoS One Research Article 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. Public Library of Science 2014-09-12 /pmc/articles/PMC4162618/ /pubmed/25216250 http://dx.doi.org/10.1371/journal.pone.0107590 Text en © 2014 Brown et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Brown, Thomas I.
Collie, David S.
Shaw, Darren J.
Rzechorzek, Nina M.
Sallenave, Jean-Michel
Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator
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
title_full Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator
title_fullStr Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator
title_full_unstemmed Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator
title_short Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator
title_sort sheep lung segmental delivery strategy demonstrates adenovirus priming of local lung responses to bacterial lps and the role of elafin as a response modulator
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162618/
https://www.ncbi.nlm.nih.gov/pubmed/25216250
http://dx.doi.org/10.1371/journal.pone.0107590
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