Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation.
Kagan-VE; Konduru-NV; Feng-W; Allen-BL; Conroy-J; Volkov-Y; Vlasova-II; Belikova-NA; Yanamala-N; Kapralov-A; Tyurina-YY; Shi-J; Kisin-ER; Murray-AR; Franks-J; Stolz-D; Gou-P; Klein-Seetharaman-J; Fadeel-B; Star-A; Shvedova-AA
Nat Nanotechnol 2010 May; 5(5):354-359
We have shown previously that single-walled carbon nanotubes can be catalytically biodegraded over several weeks by the plant-derived enzyme, horseradish peroxidase1. 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.
Biodegradation; Biological-factors; Cell-function; Cellular-reactions; Dust-exposure; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-disorders; Lung-irritants; Molecular-biology; Particulates; Peroxidases; Physiological-effects; Pulmonary-disorders; Pulmonary-system; Respiratory-irritants
University of Pittsburgh at Pittsburgh