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Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin

Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been shown to be cytotoxic to mammalian cells in tissue and organ culture. In this study we tested the ability of recombinant CARDS (rCARDS) t...

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Autores principales: Hardy, R. Doug, Coalson, Jacqueline J., Peters, Jay, Chaparro, Adriana, Techasaensiri, Chonnamet, Cantwell, Angelene M., Kannan, T. R., Baseman, Joel B., Dube, Peter H.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762541/
https://www.ncbi.nlm.nih.gov/pubmed/19859545
http://dx.doi.org/10.1371/journal.pone.0007562
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author Hardy, R. Doug
Coalson, Jacqueline J.
Peters, Jay
Chaparro, Adriana
Techasaensiri, Chonnamet
Cantwell, Angelene M.
Kannan, T. R.
Baseman, Joel B.
Dube, Peter H.
author_facet Hardy, R. Doug
Coalson, Jacqueline J.
Peters, Jay
Chaparro, Adriana
Techasaensiri, Chonnamet
Cantwell, Angelene M.
Kannan, T. R.
Baseman, Joel B.
Dube, Peter H.
author_sort Hardy, R. Doug
collection PubMed
description Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been shown to be cytotoxic to mammalian cells in tissue and organ culture. In this study we tested the ability of recombinant CARDS (rCARDS) toxin to elicit changes within the pulmonary compartment in both mice and baboons. Animals responded to a respiratory exposure to rCARDS toxin in a dose and activity-dependent manner by increasing the expression of the pro-inflammatory cytokines IL-1α, 1β, 6, 12, 17, TNF-α and IFN-γ. There was also a dose-dependent increase in several growth factors and chemokines following toxin exposure including KC, IL-8, RANTES, and G-CSF. Increased expression of IFN-γ was observed only in the baboon; otherwise, mice and baboons responded to CARDS toxin in a very similar manner. Introduction of rCARDS toxin to the airways of mice or baboons resulted in a cellular inflammatory response characterized by a dose-dependent early vacuolization and cytotoxicity of the bronchiolar epithelium followed by a robust peribronchial and perivascular lymphocytic infiltration. In mice, rCARDS toxin caused airway hyper-reactivity two days after toxin exposure as well as prolonged airway obstruction. The changes in airway function, cytokine expression, and cellular inflammation correlate temporally and are consistent with what has been reported for M. pneumoniae infection. Altogether, these data suggest that the CARDS toxin interacts extensively with the pulmonary compartment and that the CARDS toxin is sufficient to cause prolonged inflammatory responses and airway dysfunction.
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spelling pubmed-27625412009-10-27 Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin Hardy, R. Doug Coalson, Jacqueline J. Peters, Jay Chaparro, Adriana Techasaensiri, Chonnamet Cantwell, Angelene M. Kannan, T. R. Baseman, Joel B. Dube, Peter H. PLoS One Research Article Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been shown to be cytotoxic to mammalian cells in tissue and organ culture. In this study we tested the ability of recombinant CARDS (rCARDS) toxin to elicit changes within the pulmonary compartment in both mice and baboons. Animals responded to a respiratory exposure to rCARDS toxin in a dose and activity-dependent manner by increasing the expression of the pro-inflammatory cytokines IL-1α, 1β, 6, 12, 17, TNF-α and IFN-γ. There was also a dose-dependent increase in several growth factors and chemokines following toxin exposure including KC, IL-8, RANTES, and G-CSF. Increased expression of IFN-γ was observed only in the baboon; otherwise, mice and baboons responded to CARDS toxin in a very similar manner. Introduction of rCARDS toxin to the airways of mice or baboons resulted in a cellular inflammatory response characterized by a dose-dependent early vacuolization and cytotoxicity of the bronchiolar epithelium followed by a robust peribronchial and perivascular lymphocytic infiltration. In mice, rCARDS toxin caused airway hyper-reactivity two days after toxin exposure as well as prolonged airway obstruction. The changes in airway function, cytokine expression, and cellular inflammation correlate temporally and are consistent with what has been reported for M. pneumoniae infection. Altogether, these data suggest that the CARDS toxin interacts extensively with the pulmonary compartment and that the CARDS toxin is sufficient to cause prolonged inflammatory responses and airway dysfunction. Public Library of Science 2009-10-27 /pmc/articles/PMC2762541/ /pubmed/19859545 http://dx.doi.org/10.1371/journal.pone.0007562 Text en Hardy 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
Hardy, R. Doug
Coalson, Jacqueline J.
Peters, Jay
Chaparro, Adriana
Techasaensiri, Chonnamet
Cantwell, Angelene M.
Kannan, T. R.
Baseman, Joel B.
Dube, Peter H.
Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin
title Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin
title_full Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin
title_fullStr Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin
title_full_unstemmed Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin
title_short Analysis of Pulmonary Inflammation and Function in the Mouse and Baboon after Exposure to Mycoplasma pneumoniae CARDS Toxin
title_sort analysis of pulmonary inflammation and function in the mouse and baboon after exposure to mycoplasma pneumoniae cards toxin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762541/
https://www.ncbi.nlm.nih.gov/pubmed/19859545
http://dx.doi.org/10.1371/journal.pone.0007562
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