Use of nasal epithelium as a minimally invasive surrogate for testing acid sphingomyelinase activity through thermal burn injury-induced microvesicle particle release

Skin keratinocyte acid sphingomyelinase (ASM) is critical in the generation of subcellular microvesicle particles (MVP) implicated in skin responses to multiple environmental stressors including ultraviolet B radiation and thermal burn injury (TBI). Additionally, ASM is a pharmacologic target to potentially treat many systemic conditions from metabolic disorders to viral infections. Yet, the ability to confirm ASM inhibition is a therapeutic gap. The current studies sought to test if nasal epithelium could serve as a minimally invasive test for ASM activity by using MVP release. For these studies we obtained nasal epithelial washes from human volunteers and treated them ex vivo with an experimental TBI with MVP quantified to asses ASM activity. Epithelial cells were obtained from 20 healthy adult volunteers using a nasal brush. Histologic characterization and pan-cytokeratin staining revealed approximately equal numbers of epithelial and goblet cells. Treatment of the fresh epithelial cells with an experimental TBI resulted in fairly reproducible increased numbers of MVP blocked by ASM inhibitors imipramine and amitriptyline. These studies provide a simple methodology that could be used to assess ASM inhibitory effects of systemic agents that may possibly be employed to treat ASM-associated pathologic conditions including photosensitivity, acute TBI and viral infections including COVID. Oral treatment with acid sphingomyelinase inhibitors is a potential therapeutic avenue for skin disorders. The ability to directly assess the level of acid sphingomyelinase inhibition is a methodologic gap. The current studies suggest harvesting nasal epithelium to measure microvesicle particle release could provide a needed methodology to address this concern.