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Modulation of Human Dendritic Cell Activity by Adsorbed Fibrin(ogen)

Thacker, Robert I.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218553202

Abstract Details

2008, PhD, University of Cincinnati, Medicine : Pathobiology and Molecular Medicine.
Fibrinogen, a plasma protein central to clot formation, has long been considered to play a role in inflammation and immunity. Fibrin(ogen) interactions with various immune cells have been heavily investigated; lacking is an understanding of the protein's influence on dendritic cell activity. Results from Chapter 2 demonstrate that fibrinogen initiates human dendritic cell production of inflammatory cytokines and chemokines. Adsorbed fibrin(ogen) has increased stimulatory capacity over fibrin(ogen) free in solution, indicating the bound protein, acting through the ß2-integrins, is the active species. Adsorbed fibrin(ogen) also stimulates the focal accumulation of dendritic cells. This is likely due to ß2-integrin-mediated chemotaxis of dendritic cells toward released chemokines and fibrin(ogen) degradation fragments. Because studies suggested adsorbed fibrinogen might be exploited to enhance vaccine adjuvanticity, fibrinogen-coated olive oil droplets were investigated as vaccine adjuvant. Results from Chapter 3 demonstrate the importance of surface in adjuvant activity, and the possible use of olive oil droplets as a safe and effective vaccine adjuvant. Having investigated the interactions between fibrinogen-coated particles and human dendritic cells, Chapter 4 describes the existence of a not yet recorded phenomenon: extracellular transport of cell-sized particles by dendritic cells. Results presented in that chapter not only demonstrate particles can be carried extracellularly by dendritic cells, but also that the process can be directed. Adsorbed fibrin(ogen) appears to enhance particle/dendritic cell interactions mediated through the ß2-integrins. The influence of adsorbed fibrin(ogen) on dendritic cells provides new knowledge into the protein's involvement in initiating inflammatory and immune responses, knowledge that may be applied to the development of new therapeutics to treat and prevent disease.
Gregory Retzinger, MD,PhD (Committee Chair)
Alison Weiss, PhD (Committee Member)
George Deepe, MD (Committee Member)
Judith Rhodes, PhD (Committee Member)
Philip Howles, PhD (Committee Member)
173 p.
Immunology; Pathology
fibrinogen; surfaces; inflammation; CD18; vaccine adjuvants; oil emulsion; dendritic cell; extracellular translocation; cancer metastasis; dendritic cell migration; olive oil; integrins; cytokine; chemokines

Recommended Citations

Citations

  • Thacker, R. I. (2008). Modulation of Human Dendritic Cell Activity by Adsorbed Fibrin(ogen) [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218553202

    APA Style (7th edition)

  • Thacker, Robert. Modulation of Human Dendritic Cell Activity by Adsorbed Fibrin(ogen). 2008. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218553202.

    MLA Style (8th edition)

  • Thacker, Robert. "Modulation of Human Dendritic Cell Activity by Adsorbed Fibrin(ogen)." Doctoral dissertation, University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218553202

    Chicago Manual of Style (17th edition)

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© 2008, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.