Particle‐induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

Saber, Anne Thoustrup; Jacobsen, Nicklas Raun; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O.; Halappanavar, Sabina; Yauk, Carole L.; Wallin, Håkan; Vogel, Ulla

doi:10.1002/wnan.1279

Cited by 98 publications

(144 citation statements)

References 99 publications

(252 reference statements)

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Unmodified HNTs have shown to induce very low cytotoxicity in the following human cell types: carcinoma cells, peripheral blood lymphocytes, primary umbilical vein endothelial cells, intestinal cells, and epithelial cells (Ahmed et al, 2015;Vergaro et al, 2010;Nan et al, 2008;Lai et al, 2013). However, as HNTs have similar dimensions as short carbon nanotubes (CNTs), they may potentially cause pulmonary inflammation and acute phase response following pulmonary exposure as previously reported for CNTs (Saber et al, 2013(Saber et al, , 2014Poulsen et al, 2015Poulsen et al, , 2017Jaurand, 2017).…”

Section: Introductionmentioning

confidence: 81%

“…Gebel et al (2014) proposed that biodurable HARN that do not meet the fiber paradigm may be classified as granular biodurable particles (GBPs). GBPs are classified as low toxicity particles, which may however cause inflammation and acute phase response (Moreno-Horn and Gebel, 2014;Saber et al, 2014), which in turn are risk factors for cardiovascular disease (Saber et al, 2014). Stanton et al (1981) showed that pleural dose to 40 mg of two different types of HNTs in hardened gelatin implanted on to the pleural surface resulted in formation of pleural sarcomas in 9 of 53 rats (17%) 2 years post-exposure as compared to 3 of 488 sham-treated controls (0.6%).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

et al. 2018

Self Cite

View full text Add to dashboard Cite

A B S T R A C THalloysite nanotubes (HNTs) are abundant naturally-occurring hollow aluminosilicate clay mineral fibers with a typical diameter < 100 nm and an aspect ratio of up to 200. Here we assessed the potential inhalation exposure to HNTs in an industrial research laboratory. Inside a fume hood, ten times 100 g of HNTs were poured at rate of 0.5 kg min . Inside the fume hood, the respirable mass concentration was 143 μg m −3 including background particles.Outside the fume hood we did not measure elevated concentrations. We classified 1895 particles according to their length and aspect ratio. Five particles were in aspect ratio > 3 and in length > 2 μm. These particles were agglomerated and/or aggregated particles where the longest individual fiber was 2 μm in length. The occupational exposure limits for refractory mineral fibers vary from 0.1 to 2 fibers cm −3. Following standard protocols for fiber analysis, detection of 0.1 fibers cm −3 would require analysis on 4 × 10 4 images when the filter loading is good. Thus, the fiber sampling and quantification procedures needs to be improved significantly if nanofibers < 100 nm in diameter are included in regulatory exposure assessment. Due to very limited toxicological information of HNTs we recommend avoiding inhalation exposure.

show abstract

Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…8,41,42 In contrast to CRP, SAA is more often discussed as causal factor for cardiovascular disease. 15,16,43 Furthermore, SAA exhibits pro-inflammatory characteristics such as the attraction of phagocytes, the induction of proinflammatory cytokines and the delay of neutrophil apoptosis, 11,12 which may contribute to the pathogenesis of atherosclerosis. SAA has been reported to act pro-atherogenic also by driving an increase in vascular biglycan content, predisposing the vessel wall to increased retention of atherogenic lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes

Baumann

Gube

Markert

et al. 2017

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

Zinc-and copper-containing welding fumes increase systemic C-reactive protein (CRP). The aim of this study was to investigate the performance of the biomarkers serum amyloid A (SAA) and soluble vascular cell adhesion molecule-1 (VCAM-1) in this regard. Fifteen male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc for 6 h. Plasma samples were collected before, 6 and 24 h after start of exposure and biomarkers therein were measured by electrochemiluminescent assay. For each exposure, systemic concentrations of systemic SAA, but not VCAM-1, increased significantly at 24 h after exposure start compared with baseline ("copper only": P = 0.0005, "zinc only": P = 0.027, "copper and zinc": P = 0.001). SAA showed a wider range of concentrations than did CRP and its levels increased up to 19-fold after welding fume exposure. The recognition of copper as a potential harmful component in welding fumes, also independent from zinc, deserves further consideration. SAA might represent a new sensitive biomarker for potential subclinical sterile inflammation after inhalation of copper-and/or zinc-containing welding fumes. As elevations of CRP and SAA protein have both been linked to a higher risk for cardiovascular disease, these findings might particularly be important for long-term welders. Journal of Exposure Science and Environmental Epidemiology INTRODUCTIONA large number of workers are exposed to welding fumes containing various types of gases and metal particles in occupational settings. Depending on the constitution of the welding fumes and the respective exposure conditions, epidemiological studies have shown that welding fume exposure is associated with the risk of health impairment through respiratory illness, inflammation and cardiovascular disease. [1][2][3][4] Zinc and copper play an increasing role in modern joining technology, especially in the automotive industry, and hence exposures from workers become more frequent. In a recent study, a distinct increase of systemic C-reactive protein (CRP) has been shown after inhalation of welding fume from a metal inert gas brazing process of zinc-coated steel using a copper-containing welding wire at an average fume concentration of 2.5 mg/m 3 . 5 A further study tested the effect of elevated systemic CRP levels after exposure with three different doses of this welding fume and found increases of CRP after exposure with 2.0 and 2.5 mg/m 3 average fume concentration, but not at 1.4 mg/m 3 . Hence, it was concluded that the no-observed-effect level for systemic inflammation after such exposures was 1.4 mg/m 3 and the lowest observed effect level was 2.0 mg/m 3 . 6 This corresponds to zinc concentrations of 0.84 mg/m 3 and 1.2 mg/m 3 , respectively, and copper concentrations of 0.24 mg/m 3 and 0.34 mg/m 3 , respectively. 6 A subsequent third study showed that the observed effects were due to the zinc as well as copper present in the welding fume, as the welding fumes which contained either zinc and no cop...

show abstract

“…Inflammation was determined as the influx of inflammatory cells in the lung lining fluid [by the cellular composition in the bronchoalveolar lavage (BAL) fluid (BALF)], and BALF protein concentration was assessed as a general marker of lung tissue damage. Saa3 mRNA levels in lung and Saa1 levels in liver were used as biomarkers for acute phase response (24–26). Genotoxicity was assessed as DNA strand breaks determined by comet assay in BAL cells, lung and liver.…”

Section: Introductionmentioning

confidence: 99%

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice

Wallin

Kyjovska

Poulsen

et al. 2016

MUTAGE

Self Cite

View full text Add to dashboard Cite

The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mRNA levels in liver tissue by real-time quantitative polymerase chain reaction. Instillation of NRCWE-001 and -002 both induced a dose-dependent neutrophil influx into the lung lining fluid and Saa3 mRNA levels in lung tissue at all assessed time points. There was no statistically significant difference between NRCWE-001 and NRCWE-002. Exposure to both TiO2 NPs induced increased levels of DNA strand breaks in lung tissue at all doses 1 and 28 days post-exposure and NRCWE-002 at the low and middle dose 3 days post-exposure. The DNA strand break levels were statistically significantly different for NRCWE-001 and -002 for liver and for BAL cells, but no consistent pattern was observed. In conclusion, functionalisation of reactive negatively charged rutile TiO2 to positively charged did not consistently influence pulmonary toxicity of the studied TiO2 NPs.

show abstract

Particle‐induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

Cited by 98 publications

References 99 publications

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice

Contact Info

Product

Resources

About

Particle‐induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

Cited by 98 publications

References 99 publications

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes

Surface modification does not influence the genotoxic and inflammatory effects of TiO2nanoparticles after pulmonary exposure by instillation in mice

Contact Info

Product

Resources

About

Surface modification does not influence the genotoxic and inflammatory effects of TiO₂nanoparticles after pulmonary exposure by instillation in mice