Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes

Our plain-English summary of Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes, by S.I. Sinis, C. Hatzoglou, K.I. Gourgoulianis, et al (Frontiers in Physiology, 2018).

The study

• Authors: S.I. Sinis, C. Hatzoglou, K.I. Gourgoulianis, S.G. Zarogiannis
• Journal: Frontiers in Physiology
• Published: 2018;9:295
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Nanoparticles have great potential for numerous applications due to their unique physicochemical properties. However, concerns have been raised that they may induce deleterious effects on biological systems. There is accumulating evidence that, like asbestos, inhaled nanomaterials of >5 μm and high aspect ratio (3:1), particularly rod-like carbon nanotubes, may inflict pleural disease including mesothelioma. Additionally, a recent set of case reports suggests that inhalation of polyacrylate/nanosilica could in part be associated with inflammation and fibrosis of the pleura of factory workers. However, the adverse outcomes of nanoparticle exposure to mesothelial tissues are still largely unexplored. In that context, the present review aims to provide an overview of the relevant pathophysiological implications involving toxicological studies describing effects of engineered nanoparticles on mesothelial cells and membranes. In vitro studies primarily emphasize on simulating cellular uptake and toxicity of nanotubes on benign or malignant cell lines. On the other hand, in vivo studies focus on illustrating endpoints of serosal pathology in rodent animal models. From a molecular aspect, some nanoparticle categories are shown to be cytotoxic and genotoxic after acute treatment, whereas chronic incubation may lead to malignant-like transformation. At an organism level, a number of fibrous shaped nanotubes are related with features of chronic inflammation and MWCNT-7 is the only type to consistently inflict mesothelioma.

In plain English

This was a review of published toxicological studies on the effects of engineered nanoparticles, mainly carbon nanotubes, on mesothelial cells and mesothelial membranes. Two of the authors searched PubMed in August 2017, retrieving 508 unique papers of which 55 were eligible. The review covered laboratory work on uptake, cell damage and DNA damage in mesothelial cell lines (such as MeT5A, MESO-1, LP9). It also covered rodent studies that used inhalation, intratracheal instillation, intrapulmonary spraying, and intrapleural or intraperitoneal injection, some of which included comparisons with asbestos (crocidolite, amosite). Among the findings described: MWCNTs in gelatin and DPPC decreased MESO-1 viability by 38 and 83%; chronic SWCNT and MWCNT exposure raised MMP-2 mRNA 51-fold and 23-fold in MeT5A cells; and intrapulmonary spraying of MWCNT-N gave mediastinal mesothelioma in 6/38 rats versus none of 28 controls. In one intraperitoneal study, mesothelioma rates for four MWCNT types ranged from 98% (type A, high dose) to 40% (type D, low dose), against 66% in the amosite asbestos group. The authors concluded that only MWCNT-7 is consistently shown to induce mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review of published in vitro and in vivo toxicological studies, with stated inclusion criteria and PubMed search terms
• Who was studied: Published toxicological studies identified by a PubMed search carried out by two authors in August 2017; 508 unique papers retrieved, 55 eligible; studies used mesothelial cell lines and rodent models
• Exposure: Engineered nanoparticles, chiefly single- and multi-walled carbon nanotubes (including MWCNT-7 and MWCNT-N), plus nickel and silver nanoparticles/nanowires, graphene nanoplatelets and polyacrylate/nanosilica; some reviewed studies included asbestos (crocidolite, amosite) for comparison
• Main results:
  • In a reviewed in vitro study, MWCNTs dispersed in gelatin and in DPPC reduced MESO-1 cell viability by 38 and 83% respectively, while those in carboxylmethyl cellulose did not enter the cells
  • After chronic (up to 4 months) incubation of MeT5A mesothelial cells, MMP-2 mRNA expression rose 51-fold with SWCNTs and 23-fold with MWCNTs
  • In rats given MWCNT-N by transtracheal intrapulmonary spraying and followed for 109 weeks, mesothelioma of the mediastinal space occurred in 6/38, with no respiratory tumours in 28 vehicle/untreated control rats
  • After intraperitoneal injection of four MWCNT types of decreasing linearity (A to D), mesothelioma rates for the high-dose and low-dose groups were 98% and 90% (A), 90% and 92% (B), 94% and 84% (C), and 70% and 40% (D)
  • In the same intraperitoneal study, 66% of animals in the amosite asbestos group had a malignancy, with a mean survival time of 623 days
  • In the reviewed 104-week inhalation study of MWCNT-7 in rats, mesothelial hyperplasia and focal fibrosis of the parietal pleura increased at 2 mg/m3 in males, but no pleural mesothelioma was found
  • In the 104-week MWCNT-7 inhalation study, fibre numbers in pleural lavage fluid rose with exposure concentration in both sexes
• The authors' conclusion: The authors concluded that further study of nanoparticle risk to mesothelial cells and the pleura is needed. In their view, at present only MWCNT-7 is consistently shown to induce mesothelioma, while other fibrous CNTs and silver and nickel nanowires are associated with inflammatory features. They also concluded that tangled or aggregated CNTs are more likely to behave like granular particles with negligible carcinogenicity
• Limitations the authors state:
  • The authors state that the reviewed in vitro experimental designs were heterogeneous in endpoints, exposure duration, nanoparticle type and dispersion method
  • The authors state that dosimetry in the reviewed in vitro studies is difficult and that short exposures are unlikely to simulate naturally occurring exposure
  • The authors state that bolus instillation and intrapulmonary spraying, unlike inhalation, may overwhelm lung defences and produce exaggerated responses
  • The authors call for future animal studies to refine dosing, use well characterized asbestos controls and extend follow-up
  • The authors state that rodent models do not accurately reproduce human physiology and pathophysiology of nanoparticle exposure, injury and clearance

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Aspect Ratio (Length-to-diameter ratio), Mesothelioma, Inflammation, Fibrosis, Pleura, Pathology, Chronic Inflammation.

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• 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 — F.A. Murphy, A. Schinwald, et al. (2012)
• Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells — K. Maruyama, H. Haniu, et al. (2015)
• Chronic exposure to carbon nanotubes induces invasion of human mesothelial cells through matrix metalloproteinase-2 — W. Lohcharoenkal, L. Wang, et al. (2013)
• Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure — L. Ju, W. Wu, et al. (2017)

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