Inflammatory Responses to Zn/Cu-Containing Welding Fume in Human Alveolar Epithelial and Macrophage Cell Lines, with MIP-1β/CCL4 as a Much More Sensitive Macrophage Activation Marker than IL-8 and TNF-α

Zinc (Zn)- and copper (Cu)-containing welding fumes elevate inflammatory markers (CRP, TNF-α, IL-6, IL-8) in healthy individuals and welders. Zn- and Cu-containing nanoparticles are toxic to human macrophages. Therefore, ZnO exposure limits are under discussion. In this study, the effects of Zn/Cu-containing welding fume suspensions on A549 alveolar epithelial cells (exposure concentrations: 0.01/0.1/1/10/100 µg/mL) and THP-1 macrophages (additionally 0.001 µg/mL) were investigated over a period of 48 h. Effects on apoptosis, cytotoxicity, genotoxicity, superoxide dismutase (SOD) activity, and cytokine levels (IL-6, IL-8, MIP-1β/CCL4, TNF-α) were evaluated. Welding fume exposure increased SOD activity, and it increased Annexin-V binding and cytotoxicity effects starting at 10 µg/mL in A549 cells and particularly in THP-1 macrophages. A549 cells showed increased IL-6 at 10 and 100 µg/mL, and significant IL-8 release occurred at 10 µg/mL for A549 and 0.1 µg/mL for macrophages. Exposed macrophages released TNF-α at 1 µg/mL after 24 and 48 h and MIP-1β/CCL4 at 0.01 µg/mL after 6 h and at 0.001 µg/mL after 48 h. No genotoxic effects were detected. MIP-1β/CCL4 is a sensitive new biomarker for human macrophages exposed to Zn/Cu-containing welding fumes. The findings suggest that Zn/Cu particles affect lung cells already at doses below current occupational thresholds.