MRC Centre for Inflammation Research, Queen's Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.
Thromb Haemost. 2010 Apr;103(4):797-807. doi: 10.1160/TH09-06-0413. Epub 2010 Feb 19.
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.
空气中颗粒物质的低质量环境暴露与动脉粥样血栓形成事件有关，这可能是燃烧衍生的纳米颗粒含量的结果。人们还担心制造的纳米颗粒对心血管系统的潜在影响。为了更好地了解有毒空气颗粒如何影响心血管功能，我们利用斑马鱼作为一种可遗传操作的模型。使用光和共聚焦荧光视频显微镜，我们测量了暴露于多种有毒和无毒微粒和纳米颗粒的斑马鱼幼虫的心率和背部主动脉和尾动脉的血流。发现柴油机排气颗粒（DEP）、羧基化乳胶珠（carboxy-beads）和有毒氧化铝（Taimicron TM300），而不是无毒氧化铝（Baikalox A125），可促进皮肤和肠道细胞损伤，增加白细胞侵入表皮，尾部肌肉缺血和尾动脉止血在自由游动的斑马鱼幼虫中。系统水中存在亚硫酸钠（一种还原剂）或华法林（一种抗凝剂）可消除有毒氧化铝和羧基化乳胶珠的作用，但不能消除 DEP 的作用。皮肤屏障功能的遗传操作增强了皮肤损伤和止血作用，即使对于无毒的氧化铝也是如此。即使白细胞数量因 Pu.1 抗 MOR 而耗尽，羧基化乳胶珠的毒性作用仍然明显。我们得出结论，颗粒穿过皮肤上皮和肠道黏膜屏障的摄取，或白细胞的存在，不是颗粒诱导止血所必需的，而受损的皮肤屏障功能加重了组织损伤和止血作用。
