Effects of chemical composition on the lung cell response to coal particles: Implications for coal workers' pneumoconiosis

Abstract

Background and objective: Coal mine dust has a complex and heterogeneous chemical composition. It has been suggested that coal particle chemistry plays a critical role in determining the pathogenesis of coal workers' pneumoconiosis (CWP). In this study, we aimed to establish the association between the detrimental cellular response and the chemical composition of coal particles.

Methods: We sourced 19 real-world coal samples. Samples were crushed prior to use to minimize the impact of particle size on the response and to ensure the particles were respirable. Key chemical components and inorganic compounds were quantified in the coal samples. The cytotoxic, inflammatory and pro-fibrotic responses in epithelial cells, macrophages and fibroblasts were assessed following 24 h of exposure to coal particles. Principal component analysis (PCA) and stepwise regression were used to determine which chemical components of the coal particles were associated with the cell response.

Results: The cytotoxic, inflammatory and pro-fibrotic response varied considerably between coal samples. There was a high level of collinearity in the cell responses and between the chemical compounds within the coal samples. PCA identified three factors that explained 75% of the variance in the cell response. Stepwise multiple regression analysis identified K₂ O (p <0.001) and Fe₂ O₃ (p = 0.011) as significant predictors of cytotoxicity and cytokine production, respectively.

Conclusion: Our data clearly demonstrate that the detrimental cellular effects of exposure to coal mine dusts are highly dependent on particle chemistry. This has implications for understanding the pathogenesis of CWP.

Keywords: coal chemistry; coal workers' pneumoconiosis; cytotoxicity; fibroblast response; inflammatory response.

FIGURE 1

Representative images showing particle size at two different magnifications (scale bars represent 100 and 5 μm)

FIGURE 2

Cellular response. Cytotoxicity and cytokine production were assessed in in A549 (A) and THP‐1 cells (B), while proliferation and collagen production were quantified in CRL‐1490 cells (C) in response to 19 different coal samples. *p <0.05, compared to the control group. The overall ANOVA p‐values are shown in the graph. Values are mean (SD) with n = 6 per group for A549 and n = 7 per group for THP‐1 and CRL‐1490 cells. LDH, lactate dehydrogenase; PC, positive control for LDH assay

FIGURE 3

Correlation between particle constituents and cellular response. The correlation matrix shows the correlations between coal compositions and scores PC1, PC2 and PC3 which reflect cell cytotoxicity, the inflammatory response and fibrotic response, respectively. Each cell in the table shows the correlation coefficients between the two variables, with the corresponding colour intensity indicating the strength of the association. Numbers in bold indicate a significant correlation between the two variables (p <0.05). PCA, principal component analysis