The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells

Carbon nanotubes (CNT) are high aspect ratio nanoparticles comprising single (SWCNT) or concentrically stacked multiwalled (MWCNT) graphene sheets rolled seamlessly into a cylinder. Their high aspect-ratio and novel properties make CNT a useful industrial material and has led to their incorporation into a wide variety of consumer products. However, as the applications of CNT continue to grow, so too does the potential for occupational inhalation exposure with obvious potential hazards for worker health [1]. The structural similarities between CNT and asbestos have raised particular concern regarding the potential pathogenicity of CNT in the lung and serosal cavities, specifically the pleural and peritoneal spaces, which are key target tissues for asbestos-related disease [2].Carbon nanotubes have been found to cause a range of pathogenic effects, oxidative stress [3] inflammation and NLRP3 inflammasome activation [4], fibrosis [5,6] and genotoxicity [7].The mesothelial lining of the pleural cavity has long been known to be particularly sensitive to asbestos exposure producing pleural effusion, pleural plaques and fibrosis [8]. Cancer arising in the mesothelial cells lining both the peritoneal and pleural cavities, mesothelioma, is a response almost unique to fibrous particles. The exact mechanisms leading to fibre-induced mesothelioma formation are unknown although fibre dimensions [9-11], biopersistence [12], the generation of reactive oxygen species (ROS) [13] and inflammation [14] have all been implicated. Due to its uniformly poor prognosis, mesothelioma is the disease of most concern when contemplating the potential toxicity of new high aspect ratio nanoparticles; pleural plaques and effusion are also a consequence of long fibre dose in the pleural space. The ability of fibres to induce an inflammatory response in the pleura has been considered to be a key mechanism in the production of mesothelioma and other pleural pathology[15,16]. A length dependent inflamm