title: Impaired clearance and enhanced pulmonary inflammatory/fibrotic response to carbon nanotubes in myeloperoxidase-deficient mice.
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.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Lab Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: Alexandr A
authors.initials: AA
authors.lastname: Kapralov
authors.forename: Wei Hong
authors.initials: WH
authors.lastname: Feng
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Murray
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.forename: Claudette M
authors.initials: CM
authors.lastname: St Croix
authors.forename: Megan A
authors.initials: MA
authors.lastname: Lang
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: Nagarjun V
authors.initials: NV
authors.lastname: Konduru
authors.forename: Brett L
authors.initials: BL
authors.lastname: Allen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Conroy
authors.forename: Gregg P
authors.initials: GP
authors.lastname: Kotchey
authors.forename: Bashir M
authors.initials: BM
authors.lastname: Mohamed
authors.forename: Aidan D
authors.initials: AD
authors.lastname: Meade
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
authors.forename: Alexander
authors.initials: A
authors.lastname: Star
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D037742:Nanotubes, Carbon / Q000633:toxicity* / Q000648:ultrastructure; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000172:deficiency* / Q000235:genetics; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D037742:Nanotubes, Carbon; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase