Receptor-mediated uptake of pepsin by laryngeal epithelial cells

Objectives: Previous data suggest a mechanistic link between exposure to pepsin and cellular changes that lead to laryngopharyngeal disorders. Initial confocal microscopy analysis of pepsin uptake by cultured hypopharyngeal epithelial cells revealed that pepsin may be taken up by a specific process. The objective of this study was to use electron microscopy to confirm the initial confocal findings and to determine whether uptake of pepsin by laryngeal epithelial cells is receptor-mediated. Methods: Cultured human hypopharyngeal FaDu cells and human laryngeal biopsy specimens, taken from the posterior larynx of control patients without symptoms or findings of laryngopharyngeal reflux, were exposed to purified human pepsin 3b with or without transferrin (a marker for receptor-mediated endocytosis) in vitro. Uptake of pepsin was documented by electron microscopy. Results: Pepsin co-localized with transferrin in intracellular vesicles; this finding confirms that pepsin is taken up by laryngeal epithelial cells by receptor-mediated endocytosis. Conclusions: This is a novel finding that further defines the role and mechanism of pepsin-mediated injury in laryngopharyngeal reflux. The objective of ongoing research is to identify the receptor and investigate potential antagonists as a new therapeutic option for patients with reflux-attributed disease - in particular, those patients who have persistent symptoms despite acid suppression therapy.