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Open Access 01-12-2017 | Research article

Pulmonary challenge with carbon nanoparticles induces a dose-dependent increase in circulating leukocytes in healthy males

Authors: Marieke Berger, Johannes D. de Boer, René Lutter, Michiel Makkee, Peter J. Sterk, Elles M. Kemper, Jaring S. van der Zee

Published in: BMC Pulmonary Medicine | Issue 1/2017

Abstract

Background

Inhalation of particulate matter, as part of air pollution, is associated with increased morbidity and mortality. Nanoparticles (< 100 nm) are likely candidates for triggering inflammatory responses and activation of coagulation pathways because of their ability to enter lung cells and pass bronchial mucosa. We tested the hypothesis that bronchial segmental instillation of carbon nanoparticles causes inflammation and activation of coagulation pathways in healthy humans in vivo.

Methods

This was an investigator-initiated, randomized controlled, dose-escalation study in 26 healthy males. Participants received saline (control) in one lung segment and saline (placebo) or carbon nanoparticles 10 μg, 50 μg, or 100 μg in the contra-lateral lung. Six hours later, blood and bronchoalveolar lavage fluid (BALF) was collected for inflammation and coagulation parameters.

Results

There was a significant dose-dependent increase in blood neutrophils (p = 0.046) after challenge with carbon nanoparticles. The individual top-dose of 100 μg showed a significant (p = 0.05) increase in terms of percentage neutrophils in blood as compared to placebo.

Conclusions

This study shows a dose-dependent effect of bronchial segmental challenge with carbon nanoparticles on circulating neutrophils of healthy volunteers. This suggests that nanoparticles in the respiratory tract induce systemic inflammation.

Trial registration

Dutch Trial Register no. 2976. 11 July 2011. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2976

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Atkinson RW, Kang S, Anderson HR, Mills IC, Walton HA. Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: a systematic review and meta-analysis. Thorax. 2014 Jul;69(7):660–5.CrossRefPubMedPubMedCentral

Lu F, Xu D, Cheng Y, Dong S, Guo C, Jiang X, et al. Systematic review and meta-analysis of the adverse health effects of ambient PM2.5 and PM10 pollution in the Chinese population. Environ Res. 2015 Jan;136:196–204.CrossRefPubMed

Rom WN, Boushey H, Caplan A. Experimental human exposure to air pollutants is essential to understand adverse health effects. Am J Respir Cell Mol Biol. 2013 Nov;49(5):691–6.CrossRefPubMedPubMedCentral

Kelly FJ, Fussell JC. Linking ambient particulate matter pollution effects with oxidative biology and immune responses. Ann N Y Acad Sci. 2015 Mar;1340:84–94.CrossRefPubMed

Patel MM, Chillrud SN, Deepti KC, Ross JM, Kinney PL. Traffic-related air pollutants and exhaled markers of airway inflammation and oxidative stress in new York City adolescents. Environ Res. 2013 Feb;121:71–8.CrossRefPubMed

Kubesch NJ, de NA WD, Martinez D, Carrasco-Turigas G, Bouso L, et al. Respiratory and inflammatory responses to short-term exposure to traffic-related air pollution with and without moderate physical activity. Occup Environ Med. 2015 Apr;72(4):284–93.CrossRefPubMed

Viehmann A, Hertel S, Fuks K, Eisele L, Moebus S, Mohlenkamp S, et al. Long-term residential exposure to urban air pollution, and repeated measures of systemic blood markers of inflammation and coagulation. Occup Environ Med. 2015 Sep;72(9):656–63.CrossRefPubMed

Franklin BA, Brook R, Arden PC III. Air pollution and cardiovascular disease. Curr Probl Cardiol. 2015 May;40(5):207–38.CrossRefPubMed

Donaldson K, Brown D, Clouter A, Duffin R, MacNee W, Renwick L, et al. The pulmonary toxicology of ultrafine particles. J Aerosol Med. 2002;15(2):213–20.CrossRefPubMed

10.

Schulz H, Harder V, Ibald-Mulli A, Khandoga A, Koenig W, Krombach F, et al. Cardiovascular effects of fine and ultrafine particles. J Aerosol Med. 2005;18(1):1–22.CrossRefPubMed

11.

Hussain S, Boland S, Baeza-Squiban A, Hamel R, Thomassen LC, Martens JA, et al. Oxidative stress and proinflammatory effects of carbon black and titanium dioxide nanoparticles: role of particle surface area and internalized amount. Toxicology. 2009 Jun 16;260(1–3):142–9.CrossRefPubMed

12.

Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdorster G, Utell MJ, et al. Ultrafine particle deposition in humans during rest and exercise. Inhal Toxicol. 2003 May;15(6):539–52.CrossRefPubMed

13.

Muller L, Riediker M, Wick P, Mohr M, Gehr P, Rothen-Rutishauser B. Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. J R Soc Interface. 2010 Feb 6;7(Suppl 1):S27–40.CrossRefPubMed

14.

Rothen-Rutishauser B, Muhlfeld C, Blank F, Musso C, Gehr P. Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model. Part Fibre Toxicol. 2007;4:9.CrossRefPubMedPubMedCentral

15.

Saber AT, Jacobsen NR, Jackson P, Poulsen SS, Kyjovska ZO, Halappanavar S, et al. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2014;6(6):517–31.

16.

Moller W, Felten K, Sommerer K, Scheuch G, Meyer G, Meyer P, et al. Deposition, retention, and translocation of ultrafine particles from the central airways and lung periphery. Am J Respir Crit Care Med. 2008 Feb 15;177(4):426–32.CrossRefPubMed

17.

Shah AP, Pietropaoli AP, Frasier LM, Speers DM, Chalupa DC, Delehanty JM, et al. Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy human subjects. Environ Health Perspect. 2008 Mar;116(3):375–80.CrossRefPubMed

18.

Horie M, Yoshiura Y, Izumi H, Oyabu T, Tomonaga T, Okada T, et al. Comparison of the Pulmonary Oxidative Stress Caused by Intratracheal Instillation and Inhalation of NiO Nanoparticles when Equivalent Amounts of NiO Are Retained in the Lung. Antioxidants (Basel). 2016;5(1).

19.

Nemmar A, Yuvaraju P, Beegam S, Yasin J, Dhaheri RA, Fahim MA, et al. In vitro platelet aggregation and oxidative stress caused by amorphous silica nanoparticles. Int J Physiol Pathophysiol Pharmacol. 2015;7(1):27–33.PubMedPubMedCentral

20.

Hoogerwerf JJ, de Vos AF, Bresser P, Van der Zee JS, Pater JM, de BA, et al. Lung inflammation induced by lipoteichoic acid or lipopolysaccharide in humans. Am J Respir Crit Care Med. 2008 Jul 1;178(1):34–41.CrossRefPubMed

21.

Julius P, Lommatzsch M, Kuepper M, Bratke K, Faehndrich S, Luttmann W, et al. Safety of segmental allergen challenge in human allergic asthma. J Allergy Clin Immunol. 2008 Mar;121(3):712–7.CrossRefPubMed

22.

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319–38.CrossRefPubMed

23.

EMA. Guideline on requirements for First-In-Man clinical trials for potential high-risk medicinal products. 23–7-2007. Ref Type: Online Source.

24.

Strak M, Steenhof M, Godri KJ, Gosens I, Mudway IS, Cassee FR, et al. Variation in characteristics of ambient particulate matter at eight locations in the Netherlands- the RAPTES project. Atmos Environ. 2011;45:4442–53.CrossRef

25.

Du Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013 Aug;68(Suppl 1):i1–i44.CrossRefPubMed

26.

Berger M, Kooyman PJ, Makkee M, Van der Zee JS, Sterk PJ, van DJ, et al. How to achieve safe, high-quality clinical studies with non-medicinal investigational products? A practical guideline by using intra-bronchial carbon nanoparticles as case study. Respir Res. 2016;17(1):102.CrossRefPubMedPubMedCentral

27.

Jacobs L, Nawrot TS, de GB MR, Degraeuwe B, Bernard A, et al. Subclinical responses in healthy cyclists briefly exposed to traffic-related air pollution: an intervention study. Environ Health. 2010;9:64.CrossRefPubMedPubMedCentral

28.

Frampton MW, Stewart JC, Oberdorster G, Morrow PE, Chalupa D, Pietropaoli AP, et al. Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Environ Health Perspect. 2006 Jan;114(1):51–8.CrossRefPubMed

29.

Kager LM, de Boer JD, Bresser P, Van der Zee JS, Zeerleder S, Meijers JC, et al. Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses. Eur Respir J. 2013 Jul;42(1):188–97.CrossRefPubMed

30.

Creutzenberg O, Bellmann B, Korolewitz R, Koch W, Mangelsdorf I, Tillmann T, et al. Change in agglomeration status and toxicokinetic fate of various nanoparticles in vivo following lung exposure in rats. Inhal Toxicol. 2012 Oct;24(12):821–30.CrossRefPubMed

31.

Husain M, Kyjovska ZO, Bourdon-Lacombe J, Saber AT, Jensen KA, Jacobsen NR, et al. Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation. Toxicol Appl Pharmacol. 2015 Dec 15;289(3):573–88.CrossRefPubMed

32.

Gardner B, Ling F, Hopke PK, Frampton MW, Utell MJ, Zareba W, et al. Ambient fine particulate air pollution triggers ST-elevation myocardial infarction, but not non-ST elevation myocardial infarction: a case-crossover study. Part Fibre Toxicol. 2014;11:1.CrossRefPubMedPubMedCentral

33.

Schreiber N, Strobele M, Kopf J, Hochscheid R, Kotte E, Weber P, et al. Lung alterations following single or multiple low-dose carbon black nanoparticle aspirations in mice. J Toxicol Environ Health A. 2013;76(24):1317–32.CrossRefPubMed

34.

Durga M, Nathiya S, Rajasekar A, Devasena T. Effects of ultrafine petrol exhaust particles on cytotoxicity, oxidative stress generation, DNA damage and inflammation in human A549 lung cells and murine RAW 264.7 macrophages. Environ Toxicol Pharmacol. 2014 Sep;38(2):518–30.CrossRefPubMed

35.

Voorhis M, Knopp S, Julliard W, Fechner JH, Zhang X, Schauer JJ, et al. Exposure to atmospheric particulate matter enhances Th17 polarization through the aryl hydrocarbon receptor. PLoS One. 2013;8(12):e82545.CrossRefPubMedPubMedCentral

36.

Langrish JP, Bosson J, Unosson J, Muala A, Newby DE, Mills NL, et al. Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms. J Intern Med. 2012 Sep;272(3):224–39.CrossRefPubMed

37.

Hatmi ZN, Saeid AK, Broumand MA, Khoshkar SN, Danesh ZF. Multiple inflammatory prognostic factors in acute coronary syndromes: a prospective inception cohort study. Acta Med Iran. 2010 Jan;48(1):51–7.PubMed

38.

Sabatine MS, Morrow DA, Cannon CP, Murphy SA, Demopoulos LA, DiBattiste PM, et al. Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes: a TACTICS-TIMI 18 (treat angina with Aggrastat and determine cost of therapy with an invasive or conservative strategy- thrombolysis in myocardial infarction 18 trial)substudy. J Am Coll Cardiol. 2002 Nov 20;40(10):1761–8.CrossRefPubMed

39.

Tanaka M, Aoki Y, Takano H, Fujitani Y, Hirano S, Nakamura R, et al. Effects of exposure to nanoparticle-rich or -depleted diesel exhaust on allergic pathophysiology in the murine lung. J Toxicol Sci. 2013 Feb;38(1):35–48.CrossRefPubMed

40.

Geiser M, Stoeger T, Casaulta M, Chen S, Semmler-Behnke M, Bolle I, et al. Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis. Part Fibre Toxicol. 2014;11:19.CrossRefPubMedPubMedCentral

41.

Zhang R, Dai Y, Zhang X, Niu Y, Meng T, Li Y, et al. Reduced pulmonary function and increased pro-inflammatory cytokines in nanoscale carbon black-exposed workers. Part Fibre Toxicol. 2014;11:73.CrossRefPubMedPubMedCentral

Title: Pulmonary challenge with carbon nanoparticles induces a dose-dependent increase in circulating leukocytes in healthy males
Authors: Marieke Berger
Johannes D. de Boer
René Lutter
Michiel Makkee
Peter J. Sterk
Elles M. Kemper
Jaring S. van der Zee
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Pulmonary Medicine / Issue 1/2017
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-017-0463-x

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