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      Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma

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          Abstract

          The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura.

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          Most cited references41

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          Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety.

          Carbon nanotubes (CNT) are an important new class of technological materials that have numerous novel and useful properties. The forecast increase in manufacture makes it likely that increasing human exposure will occur, and as a result, CNT are beginning to come under toxicological scrutiny. This review seeks to set out the toxicological paradigms applicable to the toxicity of inhaled CNT, building on the toxicological database on nanoparticles (NP) and fibers. Relevant workplace regulation regarding exposure is also considered in the light of our knowledge of CNT. CNT could have features of both NP and conventional fibers, and so the current paradigm for fiber toxicology, which is based on mineral fibers and synthetic vitreous fibers, is discussed. The NP toxicology paradigm is also discussed in relation to CNT. The available peer-reviewed literature suggests that CNT may have unusual toxicity properties. In particular, CNT seem to have a special ability to stimulate mesenchymal cell growth and to cause granuloma formation and fibrogenesis. In several studies, CNT have more adverse effects than the same mass of NP carbon and quartz, the latter a commonly used benchmark of particle toxicity. There is, however, no definitive inhalation study available that would avoid the potential for artifactual effects due to large mats and aggregates forming during instillation exposure procedures. Studies also show that CNT may exhibit some of their effects through oxidative stress and inflammation. CNT represent a group of particles that are growing in production and use, and therefore, research into their toxicology and safe use is warranted.
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            Mesothelioma epidemiology, carcinogenesis, and pathogenesis.

            The incidence of mesothelioma has gone from almost none to the current 2500-3000 cases per year in the USA. This estimate is an extrapolation based on information available from the Surveillance, Epidemiology and End Results (SEER) Program that collects information on approximately 12% of the US population. Mesothelioma is a cancer that is linked to exposure to carcinogenic mineral fibers. Asbestos and erionite have a proven causative role; the possible role of other mineral fibers in causing mesothelioma is being investigated. Asbestos is considered the main cause of mesothelioma in the US and in the Western world. The capacity of asbestos to induce mesothelioma has been linked to its ability to cause the release of TNF-alpha (that promotes mesothelial cells survival), other cytokines and growth factors, and of mutagenic oxygen radicals from exposed mesothelial cells and nearby macrophages. Some investigators proposed that as a consequence of the regulations to prevent exposure and to forbid and/or limit the use of asbestos, the incidence of mesothelioma in the US (and in some European countries) should have started to decline before or around the year 2000, and sharply decline thereafter. Unfortunately, there are no data available yet to support this optimistic hypothesis. Simian virus 40 (SV40) infection and radiation exposure are additional causes, although their contribution to the overall incidence of mesothelioma is unknown. Recent data from several laboratories indicate that asbestos exposure and SV40 infection are co-carcinogens in causing mesothelioma in rodents and in causing malignant transformation of human mesothelial cells in tissue culture. An exciting new development comes from the discovery that genetic susceptibility to mineral fiber carcinogenesis plays a critical role in the incidence of this cancer in certain families. It is hoped that the identification of this putative mesothelioma gene will lead to novel mechanistically driven preventive and therapeutic approaches.
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              The role of the diaphragm in lymphatic absorption from the peritoneal cavity.

              Lymphatics in the diaphragm form a specialised system draining fluid from the peritoneal cavity and returning it to the vascular system. Fluid enters subperitoneal lymphatic lacunae, between muscle fibres of the diaphragm, the lacunae being separated from the peritoneal cavity by a barrier comprising, successively, lymphatic endothelium, a layer of collagenous fibres, a thin fenestrated layer of elastic tissue, and the peritoneal mesothelium. To reach the lacunae, peritoneal fluid passes through stomata located between cuboidal mesothelial cells of the lacunar roof. Whilst the distribution of mesothelial stomata and subjacent lymphatic lacunae varies in different species, stomata appear to be exclusive to the diaphragm and may serve as the main drainage channels for absorption from the peritoneal cavity. Clinically, they may provide escape for tumour cells, pathogens and toxins from the peritoneal cavity. They could provide access for blood transfusions, for intraperitoneal chemotherapy to treat malignancies, and for peritoneal dialysis in treating chronic renal failure. From the lacunae, fluid traverses the diaphragm via intrinsic lymphatics to reach collecting lymphatics beneath the diaphragmatic pleura. Both intrinsic and collecting lymphatics contain valves. The collecting lymphatics drain principally into retrosternal (parasternal) lymphatic trunks that carry lymph to the great veins after it filters through mediastinal lymph nodes.
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                Author and article information

                Journal
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central
                1743-8977
                2010
                22 March 2010
                : 7
                : 5
                Affiliations
                [1 ]University of Edinburgh, Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
                Article
                1743-8977-7-5
                10.1186/1743-8977-7-5
                2857820
                20307263
                6644611d-d662-4316-94f3-fb51b1be6fde
                Copyright ©2010 Donaldson et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 December 2009
                : 22 March 2010
                Categories
                Review

                Toxicology
                Toxicology

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