Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura

Murphy, Fiona; Poland, Craig A.; Duffin, Rodger; Al‐Jamal, Khuloud T.; Ali‐Boucetta, Hanene; Nunes, António; Byrne, Fiona; Prina-Mello, Adriele; Volkov, Yuri; Li, Shouping; Mather, Stephen J.; Bianco, Alberto; Prato, Maurizio; MacNee, William; Wallace, William; Kostarelos, Kostas; Donaldson, Ken

doi:10.1016/j.ajpath.2011.02.040

Cited by 288 publications

(287 citation statements)

References 36 publications

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“…This length-dependent effect was confirmed with MWCNT-induced lesions on the inner lining of the chest wall 28 days after intrapleural exposure to MWCNTs. 26 The authors suggested that two length-dependent mechanisms are involved: (1) frustrated phagocytosis of long fibers by macrophages and (2) failure of long fibers to be cleared from the intrapleural space via stomata in the parietal pleura. 53 …”

Section: E the Effect Of Fiber Length On Cnt Potencymentioning

confidence: 99%

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

2012

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CONSPECTUSCarbon nanotubes (CNTs) are carbon atoms arranged in a crystalline graphene lattice with a tubular morphology. CNTs exhibit high tensile strength, possess unique electrical properties, are durable, and can be functionalized. These properties allow applications as structural materials, in electronics, as heating elements, in batteries, in the production of stain-resistant fabric, for bone grafting and dental implants, and for targeted drug delivery. Carbon nanofibers (CNFs) are strong, flexible fibers that are currently used to produce composite materials.Agitation can lead to aerosolized CNTs and CNFs, and peak airborne particulate concentrations are associated with workplace activities such as weighing, transferring, mixing, blending, or sonication. Most airborne CNTs or CNFs found in workplaces are loose agglomerates of micrometer diameter. However, due to their low density, they linger in workplace air for a considerable time, and a large fraction of these structures are respirable.In rat and mouse models, pulmonary exposure to single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), or CNFs causes the following pulmonary reactions: acute pulmonary inflammation and injury, rapid and persistent formation of granulomatous lesions at deposition sites of large CNT agglomerates, and rapid and progressive alveolar interstitial fibrosis at deposition sites of more dispersed CNT or CNF structures.Pulmonary exposure to SWCNTs can induce oxidant stress in aortic tissue and increases plaque formation in an atherosclerotic mouse model. Pulmonary exposure to MWCNTs depresses the ability of coronary arterioles to respond to dilators. These cardiovascular effects may result from neurogenic signals from sensory irritant receptors in the lung. Pulmonary exposure to MWCNTs also upregulates mRNA for inflammatory mediators in selected brain regions, and pulmonary exposure to SWCNTs upregulates the baroreceptor reflex. In addition, pulmonary exposure to MWCNTs may induce levels of inflammatory mediators in the blood, which may affect the cardiovascular system.

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Section: E the Effect Of Fiber Length On Cnt Potencymentioning

confidence: 99%

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

2012

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“…The characteristics of the different CNTs used have previously been reported in the literature by Wick et al [33] (SWCNT), Thurnherr et al [34] (MWCNT), Poland et al [24] (NTT, NTL) and Murphy et al [26] (NTS) and are detailed in Table 1. The key physico-chemical characteristics of each CNT are described in Table 1.…”

Section: Cnt Physico-chemical Characteristicsmentioning

confidence: 99%

“…Information related to the metal contaminants contained within the NTS sample was provided by the suppliers (Table 1). No endotoxin content, assessed by the limulous amoebocyte lysate (LAL) test, is known to be present within any of the CNT samples [10,24,26].…”

Section: Cnt Physico-chemical Characteristicsmentioning

confidence: 99%

Assessing the impact of the physical properties of industrially produced carbon nanotubes on their interaction with human primary macrophages in vitro

et al. 2013

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Abstract:Currently it is not fully understood how carbon nanotubes (CNTs) may affect human health. Despite this, CNTs are produced at a tonne mass scale yearly. Due to their large production and intended use within a variety of applications it is imperative that a clear understanding of the hazard potential of CNTs is gained. The aim of this study therefore was to assess the impact of five different industrially produced CNTs which varied in their physical properties on the viability of human monocyte derived macrophages (MDM), and subsequently, at sub-lethal concentrations (0.005-0.02 mg/mL), their ability to cause oxidative stress and a pro-inflammatory response in these important immune cells over a 24-h period. None of the CNTs caused significant cytotoxicity up to 0.02 mg/mL after 24 h. Only the long multi-walled CNTs (MWNCTs) caused a significant, dose-dependent (0.005-0.02 mg/mL) reactive oxygen species production, whilst bundled MWCNTs showed a significant tumor necrosis factor alpha release after 24 h exposure at 0.02 mg/mL. No effects were observed for either tangled MWCNTs or short MWCNTs. It can be concluded from the findings of the present study that the industrially produced CNTs studied can cause hazardous effects in vitro that may be associated with their physical properties.

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“…In addition, penetration of MWCNT administrated by pharyngeal aspiration into the pleural cavity was observed, (18) and intrapleural injection of 5 lg/mouse of MWCNT has been shown to lead to sustained inflammation and length-dependent retention of MWCNT in the pleural cavity. (19) Accordingly, direct interaction of MWCNT with the mesothelial tissue is postulated as an early pathogenic event.…”

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confidence: 99%

Multi‐walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats

et al. 2012

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Multi-walled carbon nanotubes have a fibrous structure similar to asbestos and induce mesothelioma when injected into the peritoneal cavity. In the present study, we investigated whether carbon nanotubes administered into the lung through the trachea induce mesothelial lesions. Male F344 rats were treated with 0.5 mL of 500 lg/mL suspensions of multi-walled carbon nanotubes or crocidolite five times over a 9-day period by intrapulmonary spraying. Pleural cavity lavage fluid, lung and chest wall were then collected. Multi-walled carbon nanotubes and crocidolite were found mainly in alveolar macrophages and mediastinal lymph nodes. Importantly, the fibers were also found in the cell pellets of the pleural cavity lavage, mostly in macrophages. Both multi-walled carbon nanotube and crocidolite treatment induced hyperplastic proliferative lesions of the visceral mesothelium, with their proliferating cell nuclear antigen indices approximately 10-fold that of the vehicle control. The hyperplastic lesions were associated with inflammatory cell infiltration and inflammationinduced fibrotic lesions of the pleural tissues. The fibers were not found in the mesothelial proliferative lesions themselves. In the pleural cavity, abundant inflammatory cell infiltration, mainly composed of macrophages, was observed. Conditioned cell culture media of macrophages treated with multi-walled carbon nanotubes and crocidolite and the supernatants of pleural cavity lavage fluid from the dosed rats increased mesothelial cell proliferation in vitro, suggesting that mesothelial proliferative lesions were induced by inflammatory events in the lung and pleural cavity and likely mediated by macrophages. In conclusion, intrapulmonary administration of multi-walled carbon nanotubes, like asbestos, induced mesothelial proliferation potentially associated with mesothelioma development. (Cancer Sci 2012; 103: 2045-2050 M ulti-walled carbon nanotubes (MWCNT) are structurally composed of cylinders rolled up from several layers of graphite sheets. They are several to tens of nanometers in diameter and several to tens of micrometers in length. This high length to diameter aspect ratio, a characteristic shared with asbestos fibers, has led to concern that exposure to MWCNT might cause asbestos-like lung diseases, such as lung fibrosis, lung cancer, pleural plaque and malignant mesothelioma.(1-6) Pleural plaque and malignant mesothelioma are characteristic lesions in asbestos-exposed humans. Although fiber dimensions, biopersistence, oxidative stress and inflammation have all been implicated, (7)(8)(9)(10)(11)(12) the exact mechanisms of pleural pathogenesis are unclear. According to a pathogenesis paradigm suggested by Donaldson et al.,asbestos fibers penetrate into the pleural cavity from the alveoli and deposit in the pleural tissue. Unlike spherical particles, fibrous materials such as asbestos are not cleared effectively from the pleural cavity, resulting in deposition of the fibers in the parietal pleura. This deposition, in turn, causes frustrated ...

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Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura

Cited by 288 publications

References 36 publications

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

Assessing the impact of the physical properties of industrially produced carbon nanotubes on their interaction with human primary macrophages in vitro

Multi‐walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats

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