Document Type

Honors Thesis

Major

Cellular and Molecular Biology

Advisor(s)

Julie Gosse

Committee Members

Robert Gundersen, Joshua Kelly, Jennifer Newell-Catio, Matthew Pifer

Graduation Year

May 2021

Publication Date

2025

Abstract

Cetylpyridinium chloride (CPC) is a positively charged antimicrobial in consumer products such as mouthwashes at concentrations up to 3 millimolar, thus exposing humans to high concentrations. Minimal information on eukaryotic toxicology of CPC exists; hence, there is need for information since humans and wildlife are exposed. Mast cells, ubiquitous throughout the body, are central in numerous physiological processes and diseases. We have demonstrated that CPC potently inhibits antigen-stimulated RBL-2H3 mast cell degranulation, the release of bioactive substances including histamine from intracellular granules. Degranulation inhibition occurs at non-cytotoxic CPC doses as low as 1 μM, ~1000-fold lower than the concentrations of consumer products. We have investigated the molecular mechanisms underlying the inhibition of mast cell degranulation by CPC. We have shown that CPC inhibits the antigen-stimulated influx of Ca2+, into the cytosol. Elevated Ca2+ concentration in the cytosol is reliant on ER Ca2+ stores being released and required to activate various Ca2+-dependent enzymes and processes, including microtubule polymerization. Microtubules serve as “railroad tracks” to transport the granules to the plasma membrane for fusion and degranulation. Here, we show that 10 μM CPC exposure inhibits ER Ca2+ release in a manner consistent with our hypothesis, that CPC is electrostatically interfering with signaling lipid PIP2. We also show that 5 or 10 μM CPC shuts down microtubule polymerization within 60 minutes. This research provides biochemical mechanisms underlying the effects of CPC on immune cell signaling and allows prediction of effects on disparate cell types that share similar signaling and cytoskeletal elements.

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