Monocyte chemoattractant protein-1 is critical for monocyte recruitment to the lungs in response to bacterial infection. MCP-1 is also essential for protective neutrophil recruitment to the lungs during Escherichia coli and Klebsiella pneumoniae infection. Staphylococcus aureus pneumonia, specifically strain USA300, carries a high morbidity and mortality rate and is an important pathogen in hospital/ventilator and community acquired pneumonia. In the current study, we investigated the role of MCP-1 in pulmonary innate immunity to S. aureus in C57Bl/6, MCP-1-/- and MCP-1 AB blocked mice. As compared to C57Bl/6, MCP-1-/- mice showed increased concentrations of neutrophils in the airways and lung parenchyma as assessed by nucleated cell concentrations in BALF, myeloperoxidase activity (MPO) in lung tissue, and lung histopathology, and increased concentrations of the pro-inflammatory cytokines TNF-α and IL-6. However, this increase in inflammatory cytokines and augmented neutrophilic response did not correlate with increased bacterial clearance, as determined by CFUs from BALF, lung, liver and spleen. MCP-1 AB blocked mice trended towards higher BALF nucleated cell counts and MPO activity in lung tissue, but were not significantly different from negative controls. In conclusion, MCP-1 appears to be differentially regulated during bacterial pneumonia, and in an S. aureus model, MCP-1-/- mice have moderately enhanced neutrophilic inflammation which does not improve bacterial clearance.
| Identifer | oai:union.ndltd.org:LSU/oai:etd.lsu.edu:etd-01172014-154034 |
| Date | 24 January 2014 |
| Creators | Leissinger, Mary Katherine |
| Contributors | Jeyaseelan, Samithamby, Grasperge, Britton, Gaunt, Stephen |
| Publisher | LSU |
| Source Sets | Louisiana State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lsu.edu/docs/available/etd-01172014-154034/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached herein a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to LSU or its agents the non-exclusive license to archive and make accessible, under the conditions specified below and in appropriate University policies, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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