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Characterization of a new mouse model of empyema and the mechanisms of pleural invasion by Streptococcus pneumoniae.
Am J Respir Cell Mol Biol 2012; 46(2):180-7AJ

Abstract

Although empyema affects more than 65,000 people each year in the United States and in the United Kingdom, there are limited data on the pathogenesis of pleural infection. We investigated the pathogenesis of empyema using animal and cell culture models of Streptococcus pneumoniae infection. The pathological processes during the development of empyema associated with murine pneumonia due to S. pneumoniae (strain D39) were investigated. Lungs were examined using histology, and pleural fluid and blood bacterial colony-forming units, cytokine levels, and cellular infiltrate were determined over time. Bacterial migration across mesothelial monolayers was investigated using cell culture techniques, flow cytometry, and confocal microscopy. After intranasal inoculation with 10(7) S. pneumoniae D39 strain, mice developed pneumonia associated with rapid bacterial invasion of the pleural space; raised intrapleural IL-8, VEGF, MCP-1, and TNF-α levels; and caused significant intrapleural neutrophilia followed by the development of fibrinous pleural adhesions. Bacterial clearance from the pleural space was poor, and in vitro assays demonstrated that S. pneumoniae crossed mesothelial layers by translocation through cells rather than by a paracellular route. This study describes key events during the development of S. pneumoniae empyema using a novel murine model of pneumonia-associated empyema that closely mimics human disease. The model allows for future assessment of molecular mechanisms involved in the development of empyema and evaluation of potential new therapies. The data suggest that transmigration of bacteria through mesothelial cells could be important in empyema development. Furthermore, upon entry the pleural cavity offers a protected compartment for the bacteria.

Authors+Show Affiliations

Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, 5 University Street, London, UK. jeremy.brown@ucl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21885676

Citation

Wilkosz, Sylwia, et al. "Characterization of a New Mouse Model of Empyema and the Mechanisms of Pleural Invasion By Streptococcus Pneumoniae." American Journal of Respiratory Cell and Molecular Biology, vol. 46, no. 2, 2012, pp. 180-7.
Wilkosz S, Edwards LA, Bielsa S, et al. Characterization of a new mouse model of empyema and the mechanisms of pleural invasion by Streptococcus pneumoniae. Am J Respir Cell Mol Biol. 2012;46(2):180-7.
Wilkosz, S., Edwards, L. A., Bielsa, S., Hyams, C., Taylor, A., Davies, R. J., ... Lee, Y. C. (2012). Characterization of a new mouse model of empyema and the mechanisms of pleural invasion by Streptococcus pneumoniae. American Journal of Respiratory Cell and Molecular Biology, 46(2), pp. 180-7. doi:10.1165/rcmb.2011-0182OC.
Wilkosz S, et al. Characterization of a New Mouse Model of Empyema and the Mechanisms of Pleural Invasion By Streptococcus Pneumoniae. Am J Respir Cell Mol Biol. 2012;46(2):180-7. PubMed PMID: 21885676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of a new mouse model of empyema and the mechanisms of pleural invasion by Streptococcus pneumoniae. AU - Wilkosz,Sylwia, AU - Edwards,Lindsey A, AU - Bielsa,Silvia, AU - Hyams,Catherine, AU - Taylor,Abigail, AU - Davies,Robert J O, AU - Laurent,Geoffrey J, AU - Chambers,Rachel C, AU - Brown,Jeremy S, AU - Lee,Y C Gary, Y1 - 2011/09/01/ PY - 2011/9/3/entrez PY - 2011/9/3/pubmed PY - 2012/3/27/medline SP - 180 EP - 7 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 46 IS - 2 N2 - Although empyema affects more than 65,000 people each year in the United States and in the United Kingdom, there are limited data on the pathogenesis of pleural infection. We investigated the pathogenesis of empyema using animal and cell culture models of Streptococcus pneumoniae infection. The pathological processes during the development of empyema associated with murine pneumonia due to S. pneumoniae (strain D39) were investigated. Lungs were examined using histology, and pleural fluid and blood bacterial colony-forming units, cytokine levels, and cellular infiltrate were determined over time. Bacterial migration across mesothelial monolayers was investigated using cell culture techniques, flow cytometry, and confocal microscopy. After intranasal inoculation with 10(7) S. pneumoniae D39 strain, mice developed pneumonia associated with rapid bacterial invasion of the pleural space; raised intrapleural IL-8, VEGF, MCP-1, and TNF-α levels; and caused significant intrapleural neutrophilia followed by the development of fibrinous pleural adhesions. Bacterial clearance from the pleural space was poor, and in vitro assays demonstrated that S. pneumoniae crossed mesothelial layers by translocation through cells rather than by a paracellular route. This study describes key events during the development of S. pneumoniae empyema using a novel murine model of pneumonia-associated empyema that closely mimics human disease. The model allows for future assessment of molecular mechanisms involved in the development of empyema and evaluation of potential new therapies. The data suggest that transmigration of bacteria through mesothelial cells could be important in empyema development. Furthermore, upon entry the pleural cavity offers a protected compartment for the bacteria. SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/21885676/Characterization_of_a_new_mouse_model_of_empyema_and_the_mechanisms_of_pleural_invasion_by_Streptococcus_pneumoniae_ L2 - http://www.atsjournals.org/doi/full/10.1165/rcmb.2011-0182OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -