Identifier

etd-01172014-154034

Degree

Master of Science (MS)

Department

Biomedical and Veterinary Medical Sciences - Veterinary Clinical Sciences

Document Type

Thesis

Abstract

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.

Date

2014

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Jeyaseelan, Samithamby

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