Characterization of toxicological effects of complex nano‐sized metal particles using in vitro human cell and whole blood model systems

Abstract

Metal oxide fumes form at high temperatures, for instance, during welding or firing ammunition. Inhalation exposure to high levels of airborne metal oxide particles can cause metal fume fever, cardiovascular effects, and lung damage in humans, but the associated underlying pathological mechanisms are still not fully understood. Using human alveolar epithelial cells, vascular endothelial cells, and whole blood model systems, we aimed to elucidate the short-term effects of well-characterized metal particles emitted while firing pistol ammunition. Human lung epithelial cells exposed to gunshot smoke particles (0.1-50 μg/ml) produced reactive oxygen species (ROS) and pro-inflammatory cytokines (interleukin 8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF)) that activate and recruit immune cells. Particles comprising high copper (Cu) and zinc (Zn) content activated human endothelial cells via a non-ROS-mediated mechanism that triggered immune activation (IL-8, GM-CSF), leukocyte adhesion to the endothelium (soluble intercellular adhesion molecule 1 (sICAM-1)), and secretion of regulators of the acute-phase protein synthesis (interleukin 6 (IL-6)). In human whole blood, metal oxides in gunshot smoke demonstrated intrinsic properties that activated platelets (release of soluble cluster of differentiation 40 ligand (sCD40L), platelet-derived growth factor B-chain homodimer(PDGF-BB), and vascular endothelial growth factor A (VEGF-A)) and blood coagulation and induced concomitant release of pro-inflammatory cytokines from blood leukocytes that further orchestrate thrombogenesis. The model systems applied provide useful tools for health risk assessment of particle exposures, but more studies are needed to further elucidate the mechanisms of metal fume fever and to evaluate the potential risk of long-term cardiovascular diseases.

Current research on ecotoxicity of metal-based nanoparticles: from exposure pathways, ecotoxicological effects to toxicity mechanisms

“…Its toxic effects are multifaceted and include effects on the immune system, cytotoxicity and genotoxicity. For example, copper oxide NPs are able to activate the production of reactive oxygen species and pro-inflammatory cytokines in human lung epithelial cells ( 82 ), whereas silver, gold, and platinum NPs can enter the human body through therapeutic applications and cause damage to erythrocytes, including hemolysis, agglutination, and membrane damage ( 83 ). In addition, metal-based NPs can affect the systemic system by being deposited through the respiratory tract and taken up by phagocytes in the lung ( 84 ).…”

“…The inflammatory response of ZnO NPs was also confirmed in another study ( 106 ). In addition, metal oxide NPs can activate human lung epithelial cells to produce ROS and pro-inflammatory cytokines such as interleukin 8 and granulocyte-macrophage colony-stimulating factor, which activate and recruit immune cells ( 82 ).…”