Pro-Inflammatory Effects of Inhaled Great Salt Lake Dust Particles

• Published in: Research square
• Main Authors: Cowley, Jacob M, Deering-Rice, Cassandra E, Lamb, John G, Romero, Erin G, Almestica-Roberts, Marysol, Serna, Samantha N, Sun, Lili, Kelly, Kerry E, Whitaker, Ross T, Cheminant, Jenna, Venosa, Alessandro, Reilly, Christopher A
• Format: Journal Article
• Language: English
• Published: United States 26.07.2024
• ISSN: 2693-5015
• DOI: 10.21203/rs.3.rs-4650606/v1

Climatological shifts and human activities have decimated lakes worldwide. Water in the Great Salt Lake, Utah, USA is at near record lows which has increased risks for exposure to windblown dust from dried lakebed sediments. Formal studies evaluating the health effects of inhaled Great Salt Lake dust (GSLD) have not been performed despite the belief that the dust is harmful. The objectives of this study were to illustrate windblown dust events, assess the impact of inhaled dust on the lungs, and to identify mechanisms that could contribute to the effects of GSLD in the lungs. An animation, hourly particle and meteorological data, and images illustrate the impact of dust events on the Salt Lake Valley/Wasatch front airshed. Great Salt Lake sediment and PM contained metals, lipopolysaccharides, natural and anthropogenic chemicals, and bacteria. Inhalation and oropharyngeal delivery of PM triggered neutrophilia and the expression of mRNA for , and in mouse lungs, was more potent than coal fly ash (CFA) PM , and more cytotoxic to human airway epithelial cells (HBEC3-KT) . Induction of and was replicated using HBEC3-KT and THP-1 cells. For HBEC3-KT cells, induction was variably attenuated by EGTA/ruthenium red, the TLR4 inhibitor TAK-242, and deferoxamine, while was attenuated by EGTA/ruthenium red. Inhibition of mRNA induction by EGTA/ruthenium red suggested roles for transition metals, calcium, and calcium channels as mediators of the responses. Like CFA, GSLD and a similar dust from the Salton Sea in California, activated human TRPA1, M8, and V1. However, only inhibition of TRPV1, TRPV3, and a combination of both channels impacted cytokine mRNA induction in HBEC3-KT cells. Responses of THP1 cells were partially mediated by TLR4 as opposed to TRP channels and mice expressing a "humanized" form of TRPV1 exhibited greater neutrophilia when exposed to GSLD via inhalation. This study suggests that windblown dust from Great Salt Lake and similar lake sediments could pose a risk to humans via mechanisms including the activation of TRPV1/V3, TLR4, and possibly oxidative stress.