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Lioi Dissertation.pdf (3.31 MB)

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Monocyte Activation and Membrane Disruption Mediated by Human ß-Defensin-3

Lioi, Anthony Bruno
http://rave.ohiolink.edu/etdc/view?acc_num=case1386255566

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Molecular Virology.
Human ß-defensin-3 (hBD-3) is a cationic antimicrobial peptide produced by epithelial cells. The expression of hBD-3 is markedly increased in inflammatory and disease settings including psoriasis and oral carcinoma. HBD-3 can not only kill bacteria, it can also recruit monocytes into tissues. Previous studies from our group have demonstrated that hBD-3 can activate monocytes to express the co-stimulatory molecules CD80 and CD86 in addition to various cytokines. Monocyte activation by hBD-3 has been linked to a TLR1/2-dependent signaling mechanism. Here we provide evidence that the same concentrations of hBD-3 that cause monocyte activation can also cause membrane damage in these cells via a mechanism that is dependent on cell surface expression of negatively charged phospholipids. In addition, structure/function studies of mutant hBD-3 and native hBD-3 molecules led us to discover a novel pathway of monocyte activation that may involve membrane damage and repair processes in these cells. This pathway involves the potential leakage of ATP from damaged cells that results in the activation of monocytes via the ATP-gated P2X7 ion channel. These observations define molecular mechanisms through which hBD-3 causes activation and maturation of monocytes. Further studies of these mechanisms in vivo may help to establish the potential role for hBD-3 in shaping inflammatory responses in tissues and in serving as a bridge between the innate and adaptive defenses.
Scott Sieg (Advisor)
David McDonald (Committee Chair)
Molecular Biology
Leukocytes; Defensin; Antimicrobial peptides; Monocyte activation

Recommended Citations

Citations

  • Lioi, A. B. (2014). Monocyte Activation and Membrane Disruption Mediated by Human ß-Defensin-3 [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1386255566

    APA Style (7th edition)

  • Lioi, Anthony. Monocyte Activation and Membrane Disruption Mediated by Human ß-Defensin-3. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1386255566.

    MLA Style (8th edition)

  • Lioi, Anthony. "Monocyte Activation and Membrane Disruption Mediated by Human ß-Defensin-3." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1386255566

    Chicago Manual of Style (17th edition)

case1386255566
397
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.