Impaired Clearance and Enhanced Pulmonary Inflammatory/Fibrotic Response to Carbon Nanotubes in Myeloperoxidase-Deficient Mice

Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo. Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results provide direct evidence for the participation of MPO – one of the key-orchestrators of inflammatory response – in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterials through genetic or pharmacological manipulations.

[1]  Bengt Fadeel,et al.  Close encounters of the small kind: adverse effects of man-made materials interfacing with the nano-cosmos of biological systems. , 2010, Annual review of pharmacology and toxicology.

[2]  R. Brentani,et al.  Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections , 1979, The Histochemical Journal.

[3]  C. D. Scott,et al.  Iron catalyst chemistry in modeling a high-pressure carbon monoxide nanotube reactor. , 2003, Journal of nanoscience and nanotechnology.

[4]  H. Byrne,et al.  A Systematic Study of the Dispersion of SWNTs in Organic Solvents , 2010 .

[5]  J. Crowley,et al.  Increased atherosclerosis in myeloperoxidase-deficient mice. , 2001, The Journal of clinical investigation.

[6]  P. Baron,et al.  Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[7]  Judith Klein-Seetharaman,et al.  Mechanistic investigations of horseradish peroxidase-catalyzed degradation of single-walled carbon nanotubes. , 2009, Journal of the American Chemical Society.

[8]  Lu,et al.  Fullerene pipes , 1998, Science.

[9]  Jian Qin,et al.  The importance of an endotoxin-free environment during the production of nanoparticles used in medical applications. , 2006, Nano letters.

[10]  J. Nagy,et al.  Respiratory toxicity of multi-wall carbon nanotubes. , 2005, Toxicology and applied pharmacology.

[11]  P. Nikolaev,et al.  Purification Procedures for Single-Wall Carbon Nanotubes , 2001 .

[12]  J. Klein-Seetharaman,et al.  The enzymatic oxidation of graphene oxide. , 2011, ACS nano.

[13]  R. Allen,et al.  Myeloperoxidase Selectively Binds and Selectively Kills Microbes , 2010, Infection and Immunity.

[14]  Akihiko Hirose,et al.  Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats. , 2009, The Journal of toxicological sciences.

[15]  V. I. Sergienko,et al.  Generation of Free Radicals during Decomposition of Hydroperoxide in the Presence of Myeloperoxidase or Activated Neutrophils , 2005, Biochemistry (Moscow).

[16]  Peter Wick,et al.  The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry , 2010, Journal of nanobiotechnology.

[17]  J. Tour,et al.  Longitudinal unzipping of carbon nanotubes to form graphene nanoribbons , 2009, Nature.

[18]  V. Castranova,et al.  Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos? , 2011, Toxicology and applied pharmacology.

[19]  Alexander Star,et al.  Biodegradation of single-walled carbon nanotubes through enzymatic catalysis. , 2008, Nano letters.

[20]  P. Baron,et al.  Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[21]  Judith Klein-Seetharaman,et al.  Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. , 2010, Nature nanotechnology.

[22]  Yong Zhao,et al.  Enzymatic degradation of multiwalled carbon nanotubes. , 2011, The journal of physical chemistry. A.

[23]  T. Webb,et al.  Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  Yuliang Zhao,et al.  Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. , 2005, Environmental science & technology.

[25]  Iseult Lynch,et al.  Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. , 2011, Journal of the American Chemical Society.

[26]  A. Kettle,et al.  Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. , 1998, Blood.

[27]  A. Sokolov,et al.  Myeloperoxidase-induced biodegradation of single-walled carbon nanotubes is mediated by hypochlorite , 2011, Russian Journal of Bioorganic Chemistry.

[28]  J. Hong,et al.  A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice , 2011, Archives of Toxicology.

[29]  J. Eaton,et al.  Degradation of biomaterials by phagocyte-derived oxidants. , 1993, The Journal of clinical investigation.

[30]  J. Coleman,et al.  Debundling of single-walled nanotubes by dilution: observation of large populations of individual nanotubes in amide solvent dispersions. , 2006, The journal of physical chemistry. B.