The human long noncoding RNAs CoroMarker, MALAT1, CDR1as, and LINC00460 in whole blood of individuals after controlled short-term exposure with ultrafine metal fume particles at workplace conditions, and in human macrophages in vitro.

BACKGROUND: Short-term inhalation of occupationally relevant ultrafine zinc/copper (Zn/Cu) containing welding fumes has been shown to induce subclinical systemic inflammation, associated with an elevated risk for cardiovascular diseases. The involvement of noncoding RNAs (lncRNAs) in this setting is currently unknown. However, lncRNAs have been reported to fulfill essential roles in, e.g., cardiovascular diseases, inflammation, infectious diseases, and pollution-related lung disorders. METHODS: In this study, the specific lncRNAs levels of the 4 lncRNAs CoroMarker, MALAT1, CDR1as and LINC00460 were determined by RT-qPCR in THP-1 macrophages exposed to Zn/Cu metal fume suspensions for 1, 2, and 4 hours in vitro. Furthermore, 14 subjects were exposed to Zn/Cu containing welding fumes (at 2.5 mg/m3) for 6 hours. Before, 6, 10, and 29 hours after exposure start, whole blood cell lncRNAs levels were determined by RT-qPCR. RESULTS: In THP-1 macrophages, we observed a 2.3-fold increase of CDR1as at 1 h (Wilcoxon p = 0.03), a non-significant increase of CoroMarker at 1 h, and an increase of LINC00460 at 2 h (p = 0.03) and at 4 h (p = 0.06). In whole blood cells, we determined a non-significant upregulation of CDR1as at 6 h (p = 0.2), a significant downregulation of CoroMarker at 6 h (p = 0.04), and a significant upregulation of LINC00460 levels at 10 h (p = 0.04) and 29 h (p = 0.04). MALAT-1 remained unchanged in both settings. CONCLUSION: The orientation of regulation of the lncRNAs is (except for CoroMarker) similar in the in vitro and in vivo experiments and in line with their described functions. Therefore, these results, e.g. the upregulation of the potential risk marker for cardiovascular diseases, CDR1as, contribute to understanding the underlying mechanisms of Zn/Cu-induced subclinical inflammation in metal workers.

Increased Neutrophil Granulocyte and Myeloperoxidase Levels Indicate Acute Inflammation Due to the Exposure of Zinc- and Copper-Containing Welding Fumes.

OBJECTIVE: Recent studies have shown an increase of C-reactive-protein (CRP) after exposure to zinc- and copper-containing welding fumes. The objective of this study was to determine the effects of exposure to zinc- and copper-containing welding fumes on leukocytes, their subtypes, and myeloperoxidase (MPO). METHODS: Serum samples of male volunteers were examined after exposures to welding fumes in two settings: repeated exposure on 4 consecutive days for 6 hours and single exposures for different times (3, 4, 5 hours). RESULTS: Neutrophil granulocyte and MPO levels showed increases 24 hours after single and repeated exposures for 6 hours similar to CRP increases reported in literature. Overall leukocyte levels and levels of monocytes and lymphocytes were not significantly affected. CONCLUSIONS: This study indicates the involvement of neutrophil granulocytes in welding fume fever additional to mediator related effects.

The Effects of Repeated Exposure to Zinc- and Copper-Containing Welding Fumes on Healthy Volunteers.

OBJECTIVE: Recently, the proinflammatory effects of welding fumes containing zinc and copper have been demonstrated. In the present study, it was investigated if the inflammation persists under repeated exposure. METHODS: Fifteen healthy male subjects were exposed to 6 hours of exposure with zinc- and copper-containing welding fumes on 4 consecutive days under controlled conditions. RESULTS: Inflammatory marker serum levels showed significant increases compared with baseline either 6 or 24 hours after the first exposure and stayed elevated for all following exposures. In nasal secret samples only C-reactive protein levels were increased compared with baseline. CONCLUSIONS: The current study demonstrates a persistent increase of systemic inflammatory markers indicating an elevated risk for welders chronically exposed to zinc- and copper-containing welding fumes. Topical inflammation of the upper airways did not occur.

Single and Combined Exposure to Zinc- and Copper-Containing Welding Fumes Lead to Asymptomatic Systemic Inflammation.

OBJECTIVE: Recently, it has been shown that exposure to welding fumes containing both zinc and copper leads to asymptomatic systemic inflammation in humans as shown by an increase of blood C-reactive protein. In the present study, it was investigated which metal is responsible for this effect. METHODS: Fifteen healthy male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc. RESULTS: For each exposure blood C-reactive protein increased. CONCLUSIONS: Copper- and zinc-containing welding fumes are able to induce systemic inflammation.