From U Edinburgh: The threshold length for fibre-induced acute pleural inflammation: shedding light on the early events in asbestos-induced mesothelioma

http://www.ncbi.nlm.nih.gov/pubmed/22584686

Toxicol Sci. 2012 May 12. [Epub ahead of print]

The threshold length for fibre-induced acute pleural inflammation: shedding light on the early events in asbestos-induced mesothelioma.

Schinwald A, Murphy F, Prina-Mello A, Poland C, Byrne F, Glass J, Dickerson J, Schultz D, Movia D, Jeffree C, Macnee W, Donaldson K.

Source

University of Edinburgh, Centre for Inflammation Research, United Kingdom, EH16 4TJ, 0044 131 2429201.

Abstract

Suspicion has been raised that high aspect ratio nanoparticles or nanofibres might possess asbestos-like pathogenicity. The pleural space is a specific target for disease in individuals exposed to asbestos and, by implication nanofibres. Pleural effects of fibres depends on fibre length, but the key threshold length beyond which adverse effects occur has never been identified up to now since all asbestos and vitreous fibre samples are heterogeneously distributed in their length. Nanotechnology advantageously allows for highly defined length distribution of synthetically engineered fibres which enable for in depth investigation of this threshold length. We utilised the ability to prepare silver-nanofibres of five defined length classes to demonstrate a threshold fibre length for acute pleural inflammation. Nickel-nanofibres and carbon nanotubes were then used to strengthen the relationship between fibre length and pleural inflammation. A method of intrapleural injection of nanofibres in female C57Bl/6 strain mice was used to deliver the fibre dose and we then assessed the acute pleural inflammatory response. Chestwall sections were examined by light and by scanning electron microscopy to identify areas of lesion; furthermore cell-nanowires interaction on the mesothelial surface of the parietal pleura in vivo, were investigated. Our results showed a clear threshold effect demonstrating that fibres beyond 4 µm in length are pathogenic to the pleura. The identification of the threshold length for nanofibre induced pathogenicity in the pleura has important implications for understanding the structure-toxicity relationship for asbestos-induced mesothelioma and consequent risk assessment with the aim to contribute to the engineering of synthetic nanofibres by the adoption of a benign-by-design approach.