Differences in the characteristics and pulmonary toxicity of nano- and micron-sized respirable coal dust

• Published in: Respiratory research Vol. 23; no. 1; pp. 1 - 18
• Main Authors: Zhang, Yinci, Li, Amin, Gao, Jiafeng, Liang, Jiaojiao, Cao, Niandie, Zhou, Shuping, Tang, Xiaolong
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 30.07.2022; BioMed Central; BMC
• Subjects: Acute pulmonary toxicity; Aluminum; Alveoli; Apoptosis; Biocompatibility; Biotechnology; Calcium (mitochondrial); Calcium ions; Carbon content; Cell death; Cell growth; Cell migration; Cell proliferation; Cholecystokinin; Coal; Coal ash; Coal dust; Coal dust micron particles; Coal dust nanoparticles; Coal worker’s pneumoconiosis; Collagen; Cytokines; Damage; Dust; E-cadherin; Electron microscopy; Electron paramagnetic resonance; Electron spin resonance; Enzyme-linked immunosorbent assay; Epithelial–mesenchymal transition; Extracellular matrix; Fibrosis; Flow cytometry; Fluorescent indicators; Health aspects; Immunofluorescence; Inflammation; Inflammatory response; Infrared spectroscopy; Inhalation; Interleukin 6; Laboratory animals; Lung diseases; Lungs; Membrane potential; Mesenchyme; Morphology; Nanoparticles; Oxygen; Physicochemical properties; Pneumoconiosis; Pore size; Potentiometers; Pulmonary fibrosis; Pyroptosis; Reactive oxygen species; Respiration; Scanning electron microscopy; Staining; Stimulation; Toxicity; Transforming growth factor-b1; China; United States > US; Japan
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-022-02120-8

Abstract Background The characteristics of coal dust (CD) particles affect the inhalation of CD, which causes coal worker’s pneumoconiosis (CWP). CD nanoparticles (CD-NPs, < 500 nm) and micron particles (CD-MPs, < 5 μm) are components of the respirable CD. However, the differences in physicochemical properties and pulmonary toxicity between CD-NPs and CD-MPs remain unclear. Methods CD was analyzed by scanning electron microscopy, Malvern nanoparticle size potentiometer, energy dispersive spectroscopy, infrared spectroscopy, and electron paramagnetic resonance spectroscopy. CCK-8 assay, ELISA, transmission electron microscope, JC-1 staining, reactive oxygen species activity probe, calcium ion fluorescent probe, AO/EB staining, flow cytometry, and western blot were used to determine the differences between CD-NPs and CD-MPs on acute pulmonary toxicity. CCK-8, scratch healing and Transwell assay, hematoxylin–eosin and Masson staining, immunohistochemistry, immunofluorescence, and western blot were applied to examine the effects of CD-NPs and CD-MPs on pneumoconiosis. Results Analysis of the size distribution of CD revealed that the samples had been size segregated. The carbon content of CD-NPs was greater than that of CD-MPs, and the oxygen, aluminum, and silicon contents were less. In in vitro experiments with A549 and BEAS-2B cells, CD-NPs, compared with CD-MPs, had more inflammatory vacuoles, release of pro-inflammatory cytokines (IL-6, IL-1β, TNFα) and profibrotic cytokines (CXCL2, TGFβ1), mitochondrial damage (reactive oxygen species and Ca 2+ levels and decreased mitochondrial membrane potential), and cell death (apoptosis, pyroptosis, and necrosis). CD-NPs-induced fibrosis model cells had stronger proliferation, migration, and invasion than did CD-MPs. In in vivo experiments, lung coefficient, alveolar inflammation score, and lung tissue fibrosis score (mean: 1.1%, 1.33, 1.33) of CD-NPs were higher than those of CD-MPs (mean: 1.3%, 2.67, 2.67). CD-NPs accelerated the progression of pulmonary fibrosis by upregulating the expression of pro-fibrotic proteins and promoting epithelial–mesenchymal transition. The regulatory molecules involved were E-cadherin, N-cadherin, COL-1, COL-3, ZO-1, ZEB1, Slug, α-SMA, TGFβ1, and Vimentin. Conclusions Stimulation with CD-NPs resulted in more pronounced acute and chronic lung toxicity than did stimulation with CD-MPs. These effects included acute inflammatory response, mitochondrial damage, pyroptosis, and necrosis, and more pulmonary fibrosis induced by epithelial–mesenchymal transition.