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Impaired clearance and enhanced pulmonary inflammatory/fibrotic response to carbon nanotubes in myeloperoxidase-deficient mice
Authors:Shvedova Anna A  Kapralov Alexandr A  Feng Wei Hong  Kisin Elena R  Murray Ashley R  Mercer Robert R  St Croix Claudette M  Lang Megan A  Watkins Simon C  Konduru Nagarjun V  Allen Brett L  Conroy Jennifer  Kotchey Gregg P  Mohamed Bashir M  Meade Aidan D  Volkov Yuri  Star Alexander  Fadeel Bengt  Kagan Valerian E
Affiliation:Pathology and Physiology Research Branch, Health Effects Lab Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
Abstract: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.
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