The Acute Toxicity of Mineral Fibres: A Systematic In Vitro Study Using Different THP-1 Macrophage Phenotypes

Abstract

Alveolar macrophages are the first line of defence against detrimental inhaled stimuli. To date, no comparative data have been obtained on the inflammatory response induced by different carcinogenic mineral fibres in the three main macrophage phenotypes: M0 (non-activated), M1 (pro-inflammatory) and M2 (alternatively activated). To gain new insights into the different toxicity mechanisms of carcinogenic mineral fibres, the acute effects of fibrous erionite, crocidolite and chrysotile in the three phenotypes obtained by THP-1 monocyte differentiation were investigated. The three mineral fibres apparently act by different toxicity mechanisms. Crocidolite seems to exert its toxic effects mostly as a result of its biodurability, ROS and cytokine production and DNA damage. Chrysotile, due to its low biodurability, displays toxic effects related to the release of toxic metals and the production of ROS and cytokines. Other mechanisms are involved in explaining the toxicity of biodurable fibrous erionite, which induces lower ROS and toxic metal release but exhibits a cation-exchange capacity able to alter the intracellular homeostasis of important cations. Concerning the differences among the three macrophage phenotypes, similar behaviour in the production of pro-inflammatory mediators was observed. The M2 phenotype, although known as a cell type recruited to mitigate the inflammatory state, in the case of asbestos fibres and erionite, serves to support the process by supplying pro-inflammatory mediators.

M1 macrophages deliver CASC19 via exosomes to inhibit the proliferation and migration of colon cancer cells

“…P00041, Beijing, China) and 200 ng/mL lipopolysaccharide (LPS) (Solarbio Science & Technology, cat. L8880, Beijing, China) were used to further polarised to M2 macrophages after 24h [ 13] .…”

The in vitro cytotoxic effects of natural (fibrous epsomite crystals) and synthetic (Epsom salt) magnesium sulfate

“…Mineral dust and particles of inhalable size are subjects of concern so far due to their effect on human health. Some mineral fibers such as asbestos (chrysotile, amosite, crocidolite, asbestos anthophyllite, asbestos tremolite and asbestos actinolite) and zeolites, in particular erionite, have been extensively investigated in the last decades (e.g., Cangiotti et al, 2017, 2018; Gualtieri, 2023; World Health Organization, 1986; Thompson et al, 2017; Mirata et al, 2022) and classified as a carcinogen for humans (class 1) by International Agency for Research on Cancer (IARC, 2012). For other minerals such as ferrierite (Gualtieri, 2018; Mattioli et al, 2022; Zoboli et al, 2019), mordenite (Di Giuseppe, 2020; Giordani, Ballirano, et al, 2022), offretite (Giordani et al, 2019; Mattioli et al, 2018), scolecite (Mattioli et al, 2016), mesolite and thomsonite (Betti et al, 2022; Giordani, Mattioli, et al, 2022), and others (e.g., fluoro‐edenite, winchite, richterite, clay minerals; Gianfagna et al, 2003; NIOSH, 2011; Erskine & Bailey, 2018; Larson et al, 2016), the current knowledge does not permit an accurate risk classification.…”

Identification of iron compounds in chrysotile from the Balangero mine (Turin, Italy) by micro‐Raman spectroscopy

“…[25] Currently, Balangero chrysotile is often used in in vitro studies to investigate the toxicity of asbestos, including the acute inflammatory effects. [36,44] Detecting and recognizing these impurities, especially Fe-bearing compounds, in chrysotile asbestos employed in toxicological studies could be relevant in understanding its toxicity and the mechanisms involved in Fe mobilization in chrysotile.…”