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Pulmonary exposure to carbon nanotubes promotes murine arterial thrombogenesis via platelet P-selectin

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journal contribution
posted on 23.07.2007, 09:14 by A. Nemmar, B. Nemery, P. Vandervoort, David Dinsdale, P.H.M. Hoet, M.F. Hoylaerts
Carbon nanotubes, having a diameter as small as a few nanometers, yet with robust mechanical properties, can be functionalized with chemical and biological agents and be used for the delivery of target DNA molecules or peptides into specific tissues. However, their potential adverse health effects remain unknown. Here, we studied the acute (24 h) effects of intratracheally administered (200 and 400 µg) multi-wall ground carbon nanotubes (CNT) on lung inflammation assessed by bronchoalveolar lavage (BAL), and peripheral arterial thrombogenicity in mice. The latter was evaluated from the extent of photochemically induced thrombosis in the carotid artery, measured via transillumination. I.t. instillation of CNT induced a dose-dependent influx of neutrophils in BAL, paralleled by enhanced experimental arterial thrombus formation. By flow cytometry, circulating platelet-leukocyte conjugates were found to be elevated 6 h after i.t. instillation of CNT. The pretreatment of mice with a blocking anti-P-selectin antibody prevented the formation of platelet conjugates in the circulation but did not affect neutrophil influx in the lung. Although P-selectin neutralization had no effect on the vascular injury triggered thrombus formation in saline-treated mice, it abrogated the CNT induced thrombotic amplification. We conclude that the CNT induced lung inflammation is responsible for systemic platelet activation and subsequent platelet P-selectin mediated thrombogenicity. Our findings uncover that newly engineered CNT affect not only the respiratory but also cardiovascular integrity, necessitating an evaluation of their potential risk for human health.

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Citation

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2007, 5 (6), pp.1217-1226.

Published in

JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Publisher

Blackwell

Available date

23/07/2007

Notes

This is the author's early draft (pre-modified title) of an article published in the Journal of Thrombosis and Haemostasis; http://www.blackwellpublishing.com/journal.asp?ref=1538-7933&site=1 'The definitive version is available at www.blackwell-synergy.com' http://www.blackwell-synergy.com/doi/abs/10.1111/j.1538-7836.2007.02557.x

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en

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