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Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
Inflammatory Responses to Zn/Cu-Containing Welding Fume in Human Alveolar Epithelial and Macrophage Cell Lines, with
Jan Steffens1,2, Katharina Kuth1,3, Thomas Kraus1
1Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
Abstract:
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.

