title: Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation.
abstract: We have shown previously that single-walled carbon nanotubes can be catalytically biodegraded over several weeks by the plant-derived enzyme, horseradish peroxidase. However, whether peroxidase intermediates generated inside human cells or biofluids are involved in the biodegradation of carbon nanotubes has not been explored. Here, we show that hypochlorite and reactive radical intermediates of the human neutrophil enzyme myeloperoxidase catalyse the biodegradation of single-walled carbon nanotubes in vitro, in neutrophils and to a lesser degree in macrophages. Molecular modelling suggests that interactions of basic amino acids of the enzyme with the carboxyls on the carbon nanotubes position the nanotubes near the catalytic site. Importantly, the biodegraded nanotubes do not generate an inflammatory response when aspirated into the lungs of mice. Our findings suggest that the extent to which carbon nanotubes are biodegraded may be a major determinant of the scale and severity of the associated inflammatory responses in exposed individuals.
authors.affiliation: Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. kagan@pitt.edu
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.forename: Nagarjun V
authors.initials: NV
authors.lastname: Konduru
authors.forename: Weihong
authors.initials: W
authors.lastname: Feng
authors.forename: Brett L
authors.initials: BL
authors.lastname: Allen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Conroy
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
authors.forename: Irina I
authors.initials: II
authors.lastname: Vlasova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Belikova
authors.forename: Naveena
authors.initials: N
authors.lastname: Yanamala
authors.forename: Alexander
authors.initials: A
authors.lastname: Kapralov
authors.forename: Yulia Y
authors.initials: YY
authors.lastname: Tyurina
authors.forename: Jingwen
authors.initials: J
authors.lastname: Shi
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Murray
authors.forename: Jonathan
authors.initials: J
authors.lastname: Franks
authors.forename: Donna
authors.initials: D
authors.lastname: Stolz
authors.forename: Pingping
authors.initials: P
authors.lastname: Gou
authors.forename: Judith
authors.initials: J
authors.lastname: Klein-Seetharaman
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.forename: Alexander
authors.initials: A
authors.lastname: Star
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
mesh_terms: D000818:Animals; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013059:Spectrum Analysis, Raman
chemical_list: D007074:Immunoglobulin G; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D009195:Peroxidase