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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
1   MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
,
Timothy J. A. Chico
2   MRC Centre for Developmental and Biomedical Genetics, University of Sheffield and NIHR Cardiovascular Biomedical Research Unit, Sheffield Teaching Hospitals, Sheffield, UK
,
Harriet B. Taylor
1   MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
,
Carl Tucker
3   Centre for Cardiovascular Science, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
,
Ken Donaldson
1   MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
,
Simon B. Brown
1   MRC Centre for Inflammation Research, Queen’s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
› Author Affiliations Financial support: We gratefully acknowledge technical assistance and guidance from Steve Mitchell (TEM), Steve Clarke (SEM), Craig Poland (TEM/SEM), Dr Martin Denvir (IonOptix imaging) and Dr Steve Renshaw [provision of tg(mpx::eGFP)i114 transgenic zebrafish]. This work was funded by the COLT Foundation (CF/04/07) and a Wellcome Trust ‘value in people’ award from the College of Medicine & Veterinary Medicine, University of Edinburgh.
Further Information

Publication History

Received: 29 June 2009

Accepted after major revision: 06 February 2009

Publication Date:
22 November 2017 (online)

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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 LatexTM 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
 

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