Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura
The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, especially mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomographic imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura.
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Supported in part by the Department of Health (F.A.M.); The Colt Foundation (C.A.P. and K.D.); the EC FP7 NAMDIATREAM (NMP-2009-246479) research project (F.B. and A.P.-M.) and Science Foundation Ireland, as part of the CRANN CSET-funded facilities; and the European Commission FP7 ANTICARB (HEALTH-2008-20157) research project (K.T.A.-J., A.B., M.P., and K.K.).
Author Contributions: F.A.M., C.A.P., R.D., and K.D. initiated, designed, and directed all experiments and took responsibility for planning and writing the manuscript; F.A.M., K.T.A.-J., A.N., and S.L. performed the SPECT/CT imaging experiment and analyzed the data; H.A.-B. performed transmission electron microscopy on the CNT panel; F.B., A.P.-M., and Y.V. manufactured and provided the NiNW samples and contributed to writing the manuscript; S.J.M. provided reagents and facilities for radiolabeling and SPECT/CT imaging; A.B., and M.P. prepared the short CNTs for labelling and analyzed the data; and S.L., A.B., W.M., and K.K. provided intellectual input and contributed to the writing of the manuscript.
This is an independent report commissioned and funded by the Policy Research Programme in the Department of Health. The views expressed are not necessarily those of the Department.
PII: S0002-9440(11)00274-4
doi:10.1016/j.ajpath.2011.02.040
© 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
