Publication Date

2020

Document Type

Thesis

Committee Members

Jeffrey B. Travers, M.D., Ph.D. (Advisor); Ravi P. Sahu, Ph.D. (Committee Member); Ji C. Bihl, M.D., Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Photodynamic therapy (PDT) involves the use of light at an appropriate wavelength acting on a photosensitizing chemical to cause cell death via generation of reactive oxygen species. PDT has been useful in the management of skin conditions (like acne, psoriasis) and cancers like superficial skin, esophageal and non-small cell lung cancers. In addition to these therapeutic effects, previous murine studies from our group have demonstrated that topical PDT induces immunosuppression in vivo. Thus, topical PDT of skin can generate systemic effects through unknown mechanisms. Our group showed that PDT induces an immunosuppressive effect which occurs partly via Platelet-Activating Factor Receptor (PAFR) signaling. Of importance, PAFR signaling can generate Microvesicle particles (MVP). MVPs are small extracellular membrane-enclosed particles believed to mediate cell-to-cell communication via the transport of bioactive signaling substances. The present studies tested if PDT could generate MVP release. Our studies used in vitro, ex vivo (human skin explants) and in vivo (murine) models. PDT increased MVP release across the different cell lines tested in vitro as well as treatment of human skin explants ex vivo. Murine studies also revealed a significant increase in MVP levels in skin and blood following PDT treatment. We also found a limited role for PAFR in this PDT-generated MVP release. These studies reveal a consistent production of MVPs following PDT and thus, provide insights into a possible novel mechanism whereby PDT exerts systemic effects via the generation of MVPs.

Page Count

74

Year Degree Awarded

2020

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.


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