title: Skin exposure to micro- and nano-particles can cause haemostasis in zebrafish larvae.
abstract: 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 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 haemostasis 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.
authors.affiliation: MRC Centre for Inflammation Research, Queen's Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: McLeish
authors.forename: Timothy J A
authors.initials: TJ
authors.lastname: Chico
authors.forename: Harriet B
authors.initials: HB
authors.lastname: Taylor
authors.forename: Carl
authors.initials: C
authors.lastname: Tucker
authors.forename: Ken
authors.initials: K
authors.lastname: Donaldson
authors.forename: Simon B
authors.initials: SB
authors.lastname: Brown
mesh_terms: D000537:Aluminum Oxide / Q000633:toxicity; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D007840:Latex / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008863:Microspheres; D009092:Mucous Membrane / Q000378:metabolism; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000378:metabolism / Q000633:toxicity*; D010539:Permeability; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000196:embryology / Q000378:metabolism*; D012869:Skin Absorption / Q000235:genetics; D013447:Sulfites / Q000494:pharmacology; D013997:Time Factors; D001335:Vehicle Emissions / Q000633:toxicity; D014859:Warfarin / Q000494:pharmacology; D015027:Zebrafish / Q000097:blood* / Q000196:embryology / Q000235:genetics
chemical_list: D000925:Anticoagulants; D000975:Antioxidants; D007840:Latex; D052638:Particulate Matter; D013447:Sulfites; D001335:Vehicle Emissions; D014859:Warfarin; D000537:Aluminum Oxide; C025026:sodium sulfite