Steffens Jan, Kuth Katharina, Kraus Thomas, Dott Wolfgang, Michael Sabrina, Baumann Ralf
Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
Institute for Translational Medicine, Medical Faculty, Medical School Hamburg (MSH), Am Kaiserkai 1, 20457 Hamburg, Germany.
Int J Mol Sci. 2025 Apr 18;26(8):3843. doi: 10.3390/ijms26083843.
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.
含锌（Zn）和铜（Cu）的焊接烟尘会使健康个体和焊工体内的炎症标志物（C反应蛋白、肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8）升高。含锌和铜的纳米颗粒对人类巨噬细胞有毒性。因此，氧化锌暴露限值正在讨论中。在本研究中，研究了含锌/铜的焊接烟尘悬浮液在48小时内对A549肺泡上皮细胞（暴露浓度：0.01/0.1/1/10/100微克/毫升）和THP-1巨噬细胞（另外还有0.001微克/毫升）的影响。评估了对细胞凋亡、细胞毒性、遗传毒性、超氧化物歧化酶（SOD）活性和细胞因子水平（白细胞介素-6、白细胞介素-8、巨噬细胞炎性蛋白-1β/趋化因子配体4、肿瘤坏死因子-α）的影响。焊接烟尘暴露会增加SOD活性，并且从10微克/毫升开始，它会增加A549细胞尤其是THP-1巨噬细胞中的膜联蛋白-V结合和细胞毒性作用。A549细胞在10和100微克/毫升时白细胞介素-6增加，A549细胞在10微克/毫升时以及巨噬细胞在0.1微克/毫升时会有显著的白细胞介素-8释放。暴露的巨噬细胞在24和48小时后以1微克/毫升释放肿瘤坏死因子-α，在6小时后以0.01微克/毫升释放巨噬细胞炎性蛋白-1β/趋化因子配体4，在48小时后以0.001微克/毫升释放。未检测到遗传毒性作用。巨噬细胞炎性蛋白-1β/趋化因子配体4是暴露于含锌/铜焊接烟尘的人类巨噬细胞的一种敏感的新生物标志物。研究结果表明，锌/铜颗粒在低于当前职业阈值的剂量下就已经会影响肺细胞。
