Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes

Abstract

BackgroundMulti-walled carbon nanotubes (MWCNT) are new manufactured nanomaterials with a wide spectrum of commercial applications. The durability and fiber-like dimensions (mean length 3.9 μm long × 49 nm diameter) of MWCNT suggest that these fibers may migrate to and have toxicity within the pleural region. To address whether the pleura received a significant and persistent exposure, C57BL/6J mice were exposed by pharyngeal aspiration to 10, 20, 40 and 80 μg MWCNT or vehicle and the distribution of MWCNT penetrations determined at 1, 7, 28 and 56 days after exposure. Following lung fixation and sectioning, morphometric methods were used to determine the distribution of MWCNT and the number of MWCNT fiber penetrations of three barriers: alveolar epithelium (alveolar penetrations), the alveolar epithelium immediately adjacent to the pleura (subpleural tissue), and visceral pleural surface (intrapleural space).ResultsAt 1 day 18%, 81.6% and 0.6% of the MWCNT lung burden was in the airway, the alveolar, and the subpleural regions, respectively. There was an initial, high density of penetrations into the subpleural tissue and the intrapleural space one day following aspiration which appeared to decrease due to clearance by alveolar macrophages and/or lymphatics by day 7. However, the density of penetrations increased to steady state levels in the subpleural tissue and intrapleural from day 28 - 56. At day 56 approximately 1 in every 400 fiber penetrations was in either the subpleural tissue or intrapleural space. Numerous penetrations into macrophages in the alveolar airspaces throughout the lungs were demonstrated at all times but are not included in the counts presented.ConclusionsThe results document that MWCNT penetrations of alveolar macrophages, the alveolar wall, and visceral pleura are both frequent and sustained. In addition, the findings demonstrate the need to investigate the chronic toxicity of MWCNT at these sites.

Acute pulmonary dose–responses to inhaled multi-walled carbon nanotubes

“…The MWCNT in the airways may have resulted from direct deposition from the aerosol, as well as AM moving up the mucociliary escalator as part of the clearance process. In addition, our laboratory has previously reported that after pharyngeal aspiration of MWCNT, MWCNT penetrated the pleura (Porter et al 2010;Mercer et al 2010). Lastly, our laboratory has previously reported that 56 days after pharyngeal aspiration to MWCNT that inflammation had extended to the pleura, and MWCNT had penetrated the pleura.…”

Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice

“…The mechanism of fibre translocation out of the lungs into the pleural space and into the parietal pleura and diaphragm is not known but there is a wealth of literature to support the idea that a proportion of all particles and fibres deposited in the distal region of the lungs will translocate to the pleural space (reviewed in Donaldson et al 2010). Indeed, the penetration of CNT from the lung periphery through the visceral pleura into the pleural space after aspiration exposure has been quantified by Mercer et al 2010), who determined that 0.6% of the deposited fibre burden reached the visceral pleura.…”

Potential pulmonary effects of engineered carbon nanotubes:in vitrogenotoxic effects

“…More recently, investigators have demonstrated that well dispersed MWCNT are phagocytosed by macrophages following pulmonary exposure (Porter 2009;Ryman-Rasmussen et al 2009). The macrophages containing MWCNT can migrate to the subpleural space and enter the intrapleural space as early as as one day post-exposure (Hubbs et al 2009;Mercer et al 2010;Porter et al 2010). The MWCNT penetrate the intrapleural space and induce inflammation and fibrosis in a manner similar to asbestos (Ryman-Rasmussen et al 2009).…”