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Effects of Bacterial Products on Human Blood Leukocytes
Smith, Laura Ann

2006, Master of Science in Biomedical Sciences (MSBS), University of Toledo, College of Graduate Studies.
Tumor necrosis factor alpha (TNF-alpha) is a protein that can be produced in large amounts by tissue macrophages and monocytes in response to bacterial products. Systemic release of TNF-alpha has been shown to mediate severe septic shock. Fever, hypotension, cardiovascular changes, disseminated intravascular coagulation (DIC), multiple organ failure and death are characteristics of this disease state. Our study has indicated that the bacterial products, lipopolysaccharide (LPS) and formylated peptides (fMLP), each induce activation of cytokine gene transcription in leukocytes. Interestingly, fMLP induces some intracellular signaling events that differ from those elicited by LPS. Both stimuli, however, activate the signaling pathways that converge to produce TNF-alpha. We have found that the bacterial products, fMLP and LPS, can act synergistically in the induction of TNF-alpha mRNA in monocytes, but is not seen in TNF-alpha protein levels. Our results demonstrate that multiple bacterial products may regulate the production of pro-inflammatory cytokines in a synergistic manner. Control of this inflammation is best understood at the level of synergistic regulation of intracellular signaling. Our results have also exposed a novel and potentially important pathogenic mechanism occurring during bacterial infection. Thus, our overall hypotheses are that leukocyte activation is regulated by multiple bacterial products that operate synergistically by activating multiple signaling pathways,and that this synergy is likely to play a significant role in the induction of host defense to bacterial infections and in the pathogenesis of inflammatory disorders.
Z. Kevin Pan, Ph.D. (Advisor)
95 p.

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Smith, L. (2006). Effects of Bacterial Products on Human Blood Leukocytes. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/

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Smith, Laura. "Effects of Bacterial Products on Human Blood Leukocytes." Electronic Thesis or Dissertation. University of Toledo, 2006. OhioLINK Electronic Theses and Dissertations Center. 03 Aug 2015.

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Smith, Laura "Effects of Bacterial Products on Human Blood Leukocytes." Electronic Thesis or Dissertation. University of Toledo, 2006. https://etd.ohiolink.edu/

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