Exposure to mineral fibres represents a serious occupational and environmental hazard, since it leads to chronic lung inflammation with the subsequent emergence of fibrotic pulmonary diseases, pneumoconiosis and various types of malignancies. This happens mainly by inhalation, leading to the localization of the mineral fibers in the lung tissue, where macrophages have a fundamental role in both triggering and maintaining the inflammatory response. In fact, three types of differentiated macrophages can be present at the site of injury and contribute to the outcome of the inflammatory process, namely non-activated M0, pro-inflammatory M1 and alternatively activated M2 cells. To date, no comparative data have been obtained from the concomitant analysis of the acute toxicity and the inflammatory response induced by different mineral fibres in M0, M1 and M2 cells. Thus, we set up an in vitro model based on the three macrophage phenotypes, obtained from THP-1 cell differentiation, and then employed to study the acute effects of three types of carcinogenic mineral fibres: UICC standard crocidolite, chrysotile from Balangero and fibrous erionite from Jersey. The aim of this study was to gain new insights into the different toxicity mechanisms exerted by these mineral fibres after the first 24 h of exposure. Their cytotoxic action in the three macrophage phenotypes was studied by measuring the level of cell death by either cell lysis or apoptosis. Subsequently, we studied the intracellular oxidative state, the intracellular toxic metal release, the presence of DNA damage. Moreover, the inflammatory response was assayed evaluating both the extracellular release and the gene expression profile of several pro-inflammatory cytokines known for having a crucial role in the early inflammatory response and contributing to the onset of chronic diseases and malignancies in the long term. In general, crocidolite and chrysotile were more potent with respect to erionite in triggering ROS production, apoptosis and cytokine release in the three types of differentiated macrophages. 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.
The acute toxicity of mineral fibres: a systematic in vitro study using different THP-1 macrophage phenotypes
Mirata S.;Almonti V.;Vernazza S.;Bassi A. M.;Scarfì S.;
2022-01-01
Abstract
Exposure to mineral fibres represents a serious occupational and environmental hazard, since it leads to chronic lung inflammation with the subsequent emergence of fibrotic pulmonary diseases, pneumoconiosis and various types of malignancies. This happens mainly by inhalation, leading to the localization of the mineral fibers in the lung tissue, where macrophages have a fundamental role in both triggering and maintaining the inflammatory response. In fact, three types of differentiated macrophages can be present at the site of injury and contribute to the outcome of the inflammatory process, namely non-activated M0, pro-inflammatory M1 and alternatively activated M2 cells. To date, no comparative data have been obtained from the concomitant analysis of the acute toxicity and the inflammatory response induced by different mineral fibres in M0, M1 and M2 cells. Thus, we set up an in vitro model based on the three macrophage phenotypes, obtained from THP-1 cell differentiation, and then employed to study the acute effects of three types of carcinogenic mineral fibres: UICC standard crocidolite, chrysotile from Balangero and fibrous erionite from Jersey. The aim of this study was to gain new insights into the different toxicity mechanisms exerted by these mineral fibres after the first 24 h of exposure. Their cytotoxic action in the three macrophage phenotypes was studied by measuring the level of cell death by either cell lysis or apoptosis. Subsequently, we studied the intracellular oxidative state, the intracellular toxic metal release, the presence of DNA damage. Moreover, the inflammatory response was assayed evaluating both the extracellular release and the gene expression profile of several pro-inflammatory cytokines known for having a crucial role in the early inflammatory response and contributing to the onset of chronic diseases and malignancies in the long term. In general, crocidolite and chrysotile were more potent with respect to erionite in triggering ROS production, apoptosis and cytokine release in the three types of differentiated macrophages. 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.
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