Skin exposure to micro- and nano-particles can cause haemostasis in zebrafish larvae

Jennifer A. McLeish; Timothy J. A. Chico; Harriet B. Taylor; Carl Tucker; Ken Donaldson; Simon B. Brown

doi:10.1160/TH09-06-0413

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(04): 797-807
DOI: 10.1160/TH09-06-0413

Animal Models

Schattauer GmbH

Skin exposure to micro- and nano-particles can cause haemostasis in zebrafish larvae

Jennifer A. McLeish

¹MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK

,

Timothy J. A. Chico

²MRC Centre for Developmental and Biomedical Genetics, University of Sheffield and NIHR Cardiovascular Biomedical Research Unit, Sheffield Teaching Hospitals, Sheffield, UK

,

Harriet B. Taylor

¹MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK

,

Carl Tucker

³Centre for Cardiovascular Science, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK

,

Ken Donaldson

¹MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK

,

Simon B. Brown

¹MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK

› Author Affiliations

Abstract

Summary

Low mass ambient exposure to airborne particles is associated with atherothrombotic events that may be a consequence of the combustion-derived nanoparticle content. There is concern also over the potential cardiovascular impact of manufactured nanoparticles. To better understand the mechanism by which toxic airborne particles can affect cardiovascular function we utilised zebrafish as a genetically tractable model. Using light and confocal fluorescence video-microscopy, we measured heart-rate and blood flow in the dorsal aorta and caudal artery of zebrafish larvae that had been exposed to a number of toxic and non-toxic microparticles and nanoparticles. Diesel exhaust particles (DEP), carboxy-charged Latex^TM beads (carboxy-beads) and toxic alumina (Taimicron TM300), but not non-toxic alumina (Baikalox A125), were found to promote both skin and gut cell damage, increased leukocyte invasion into the epidermis, tail muscle ischaemia and hae-mostasis within the caudal artery of free swimming zebrafish larvae. The presence of sodium sulfite, a reducing agent, or warfarin, an anticoagulant, within the system water abrogated the effects of both toxic alumina and carboxy-beads but not DEP. Genetic manipulation of skin barrier function augmented skin damage and haemostasis, even for the non-toxic alumina. The toxic effects of carboxy-beads were still apparent after leukocyte numbers were depleted with anti-Pu.1 morpholino. We conclude that particle uptake across skin epithelium and gut mucosal barriers, or the presence of leukocytes, is not required for particle-induced haemostasis while a compromised skin barrier function accentuated tissue injury and haemostasis.

Keywords

Diesel exhaust particles - nanoparticles - zebrafish - haemostasis - oxidative stress - skin

Full Text

References

References
1 Morgan WKC, Seaton A. (Eds). Occupational Lung Diseases. 3rd Edition WB Saunders; Philadelphia: 1995
2 Jansen KL, Larson TV, Koenig JQ. et al. Associations between health effects and particulate matter and black carbon in subjects with respiratory disease. Environ Health Perspect 2005; 113: 1741-1746.
3 Mills NL, Tornqvist H, Gonzalez MC. et al. Ischemic and thrombotic effects of di-lute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med 2007; 357: 1075-1082.
4 Donaldson K, Tran L, Jimenez L. et al. Combustion-derived nanoparticles: A review of their toxicology following inhalation exposure. Part Fibre Toxicol 2005; 02: 10.
5 Mills NL, Tornqvist H, Robinson SD. et al. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation 2005; 112: 3930-3936.
6 Mills NL, Tornqvist H, Robinson SD. et al. Air pollution and atherothrombosis. Inhal Toxicol 2007; 19 (Suppl. 01) 81-89.
7 Sun Q, Wang A, Jin X. et al. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. J Am Med Assoc 2005; 294: 3003-3010.
8 Lucking AJ, Lundback M, Mills NL. et al. Diesel exhaust inhalation increases thrombus formation in man. Eur Heart J 2008; 29: 3043-3051.
9 Nemmar A, Hoet PH, Dinsdale D. et al. Diesel exhaust particles in lung acutely enhance experimental peripheral thrombosis. Circulation 2003; 107: 1202-1208.
10 Suwa T, Hogg JC, Quinlan KB. et al. Particulate air pollution induces progression of atherosclerosis. J Am Coll Cardiol 2002; 39: 935-942.
11 Li Z, Hulderman T, Salmen R. et al. Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes. Environ Health Perspect 2007; 115: 377-382.
12 Erdely A, Hulderman T, Salmen R. et al. Cross-talk between lung and systemic circulation during carbon nanotube respiratory exposure. Potential biomarkers. Nano Lett 2009; 09: 36-43.
13 Hill AJ, Teraoka H, Heideman W. et al. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol Sci 2005; 86: 6-19.
14 Kreyling WG, Moller W, Semmler-Behnke M. et al. Particle dosimetry: Deposition and clearance from the respiratory tract and translocaton to extra-pulmonary sites. In: Particle Toxicology. CRC Press; Boca Raton, USA: 2007. pp 47-74.
15 Radomski A, Jurasz P, Alonso-Escolano D. et al. Nanoparticle-induced platelet aggregation and vascular thrombosis. Br J Pharmacol 2005; 146: 882-893.
16 Yamawaki H, Iwai N. Mechanisms underlying nano-sized air-pollution-mediated progression of atherosclerosis: carbon black causes cytotoxic injury/inflammation and inhibits cell growth in vascular endothelial cells. Circ J 2006; 70: 129-140.
17 Chico TJ, Ingham PW, Crossman DC. Modeling cardiovascular disease in the zebrafish. Trends Cardiovasc Med 2008; 18: 150-155.
18 Jagadeeswaran P, Gregory M, Day K. et al. Zebrafish: a genetic model for hemostasis and thrombosis. J Thromb Haemost 2005; 03: 46-53.
19 Zhu X, Zhu L, Duan Z. et al. Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to Zebrafish (Danio rerio) early developmental stage. J Environ Sci Health A Tox Hazard Subst Environ Eng 2008; 43: 278-284.
20 Nusslein-Volhard C, Dahm Zebrafish R. A practical approach. (ed 1). Oxford; Oxford University Press: 2002
21 Gray C, Packham IM, Wurmser F. et al. Ischemia is not required for arteriogenesis in zebrafish embryos. Arterioscler Thromb Vasc Biol 2007; 27: 2135-2141.
22 Renshaw SA, Loynes CA, Trushell DM. et al. A transgenic zebrafish model of neutrophilic inflammation. Blood 2006; 108: 3976-3978.
23 Denvir MA, Tucker CS, Mullins JJ. Systolic and diastolic ventricular function in zebrafish embryos: Influence of norepenephrine, MS-222 and temperature. BMC Biotechnology 2008: 8-21
24 Don Porto Carero A, Hoet PH, Verschaeve L. et al. Genotoxic effects of carbon black particles, diesel exhaust particles, and urban air particulates and their extracts on a human alveolar epithelial cell line (A549) and a human monocytic cell line (THP-1). Environ Mol Mutagen 2001; 37: 155-163.
25 Hanumanthaiah R, Thankavel B, Day K. et al. Developmental expression of vitamin K-dependent gamma-carboxylase activity in zebrafish embryos: effect of warfarin. Blood Cells Mol Dis 2001; 27: 992-999.
26 Rhodes J, Hagen A, Hsu K. et al. Interplay of pu.1 and gata1 determines myeloerythroid progenitor cell fate in zebrafish. Dev Cell 2005; 08: 97-108.
27 Brown DM, Donaldson K, Borm PJ. et al. Calcium and ROS-mediated activation of transcription factors and TNF-alpha cytokine gene expression in macrophages exposed to ultrafine particles. Am J Physiol Lung Cell Mol Physiol 2004; 286: L344-L353.
28 Dick CA, Brown DM, Donaldson K. et al. The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types. Inhal Toxicol 2003; 15: 39-52.
29 Carney TJ, von der Hardt S, Sonntag C. et al. Inactivation of serine protease Matriptase1a by its inhibitor Hai1 is required for epithelial integrity of the zebrafish epidermis. Development 2007; 134: 3461-3471.
30 Mills NL, Donaldson K, Hadoke PW. et al. Adverse cardiovascular effects of air pollution. Nat Clin Pract Cardiovasc Med 2009; 06: 36-44.
31 Duffin R, Tran L, Brown D. et al. Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 2007; 19: 849-856.
32 Abbey DE, Petersen FF, Mills PK. et al. Chronic respiratory disease associated with long-term ambient concentrations of sulfates and other air pollutants. J Expo Anal Environ Epidemiol 1993; 03 (Suppl. 01) 99-115.
33 Pelster B, Burggren WW. Disruption of hemoglobin oxygen transport does not impact oxygen-dependent physiological processes in developing embryos of zebra fish (Danio rerio). Circ Res 1996; 79: 358-362.
34 Jones G. Susceptibility to asthma and eczema from mucosal and epidermal expression of distinctive genes. Curr Allergy Asthma Rep 2007; 07: 11-17.
35 Clayton TC, Capps NE, Stephens NG. et al. Recent respiratory infection and the risk of myocardial infarction. Heart 2005; 91: 1601-1602.
36 Miano JM, Georger MA, Rich A. et al. Ultrastructure of zebrafish dorsal aortic cells. Zebrafish 2006; 03: 455-463.
37 Salvi S, Blomberg A, Rudell B. et al. Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers. Am J Respir Crit Care Med 1999; 159: 702-709.
38 Lu S, Duffin R, Poland C. et al. Efficacy of simple short-term in vitro assays for predicting the potential of metal oxide nanoparticles to cause pulmonary inflammation. Environ Health Perspect 2009; 117: 241-247.
39 Lippmann M, Ito K, Hwang JS. et al. Cardiovascular effects of nickel in ambient air. Environ Health Perspect 2006; 114: 1662-1669.
40 Yokota S, Ohara N, Kobayashi T. The effects of organic extract of diesel exhaust particles on ischemia/reperfusion-related arrhythmia and on pulmonary inflammation. J Toxicol Sci 2008; 33: 1-10.