UC Merced

Mucus rheology and mucin swelling play a critical role in maintaining respiratory health. Airway mucin hypersecretion and viscous mucus are cardinal features in chronic obstructive pulmonary disease (COPD) and are significant contributors to exacerbations and mortality. Chronic exposure to rock dust particles can potentially predispose humans to lung inflammation and increase the risk of COPD. However, the effect of rock dust particles on altering the viscoelastic properties of mucus, leading to concomitant pathological outcomes, is not clear. Studies addressing the link between the surface modification of rock dust particles and their harmful effects are also lacking. This study has examined the relationship between common rock dusts used in industry: unmodified limestone rock dust (MineBriteTM G; UCRD), modified limestone (moisture-tolerant rock dust; MTRD) and crystalline silica (Min-U-Sil®10) and their effects on mucin swelling kinetics and airway mucin rheology. To start, human lung carcinoma A549 cells were used as an in-vitro model. There was no obvious cytotoxicity of the rock dusts as determined by a cell counting kit-8 (CCK-8), and silica group showed a induced-toxicity in A549 cells after 24 h treatment. In swelling kinetics and diffusivity experiments, the modified rock dust group showed a significantly higher value as compared to the unmodified rock dust and crystalline silica groups. These results support our hypothesis that surface modification (stearic acid) can decrease metal ion leaching and thus cause fewer harmful effects on the swelling kinetics of mucins. Mucin secretion was measured using enzyme-linked lectin assay (ELLA), and the results indicated that only UCRD induced mucin secretion at higher concentration (1 mg/ml) in the A549 cells. The aggregation of mucus was monitored by measuring particle size changes using dynamic laser scattering (DLS). The unmodified rock dust group showed that, with a relatively higher concentration (0.75 mg/ml, 1.00 mg/ml), there was a significant increase in mucin aggregation. To support our swelling kinetics and mucin aggregation results, we measured the concentration of leaching metal ion by using inductively coupled plasma-optical emission spectrometry (ICP-OES). ICP-OES confirmed that calcium ions may be one of the dominant factor in the mucus aggregation and swelling kinetic experiments for both the modified and unmodified rock dusts. In addition, magnesium and iron ions were below the method detection limit. Overall, this study has demonstrated that surface modification on rock dust shows no obvious cytotoxicity and non-significant mucin aggregation. Modified rock dust provided a less harmful effect with less calcium leaching and led to a better performance on swelling and mucin secretion than unmodified rock dust.