The Threshold Length for Fiber-Induced Acute Pleural Inflammation: Shedding Light on the Early Events in Asbestos-Induced Mesothelioma

Abstract

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

A 104-week pulmonary toxicity assessment of long and short single-wall carbon nanotubes after a single intratracheal instillation in rats

“…Length is a critical factor underlying the potential toxicity of fibrous NMs (Hamilton et al, 2009;Ye et al, 1999), and fiber length is accepted as the major contributing factor to fiber pathogenicity . Therefore, we prepared a SWCNT solution containing with long fibers of a length thought to pose a potential asbestos-like hazard, based on the fiber paradigm (Donaldson et al, 2010;Murphy et al, 2012;Poland et al, 2008;Schinwald et al, 2012). The primary objective of this study was to investigate the long-term pulmonary toxicity of SWCNTs to the lungs and/or pleural tissues in rats.…”

Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice

“…Given the known health impact of mineral fibres (especially the fibrogenic and carcinogenic risk of asbestos fibres), toxicological comparisons of asbestos with fibre-like CNTs (in terms of the elongated shape) have been carried out to assess whether certain CNTs pose a similar health risk [9,11]. As a result, a threshold length of approximately 5 lm was recently suggested for nanofibre-induced acute pleural inflammation in mice [21], while a threshold CNT length exceeding 15 lm has been suggested to increase their toxic risk based on frustrated phagocytosis studies [22,23]. Determining the fibre length, however inside the lungs, remains challenging as well as whether individual tubes or even agglomerated clusters of tubes building up fibres should be considered is currently under discussion.…”

In vivo and in vitro evaluation of hydroxyapatite nanoparticle morphology on the acute inflammatory response

“…The fiber particle aspect ratio was the greatest, with a 20 to 50 fold greater particle length than width [32]. Studies have shown that fiber length and diameter are important factors in acute inflammation [57].…”