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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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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. |
format | Online Article Text |
id | pubmed-4162618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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