Inhaled Single Walled Carbon Nanotubes induce Pulmonary Inflammation in Hamsters with an Increase in 5-Lipoxygenase and Leukotriene B4 Levels.

摘要

Single walled Carbon nanotubes (SWCNTs) have wide applications in electronics and biotechnology, however SWCNTs have potential health risk associated with occupational exposure. Golden Syrian Hamsters were exposed to 1mg/m 3, 2mg/m3, and 4mg/m3 of SWCNTs for 2hrs/day for 4 consecutive days, hamsters were euthanized either 1 day or 3 day post exposure. A long duration study was carried out across 4hrs/day, for 8 or 14 consecutive days with exposure of 2mg/m3 of SWCNTs. Such groups were compared to their respective vehicle treated controls. After euthanization, lungs were either lavaged or paraffin embedded. Bronchoalveolar lavage were assessed for differential cell count, differential cell staining, 5 lipoxygenase (5 LO) activity and leukotriene B4 (LTB4) levels. Bronchoalveolar lavage cells were isolated and processed for Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM).;1mg/m3, 2mg/m3, and 4mg/m3 of SWCNTs exposure groups demonstrated significant increase levels of alveolar macrophages (2.09, 2.5, and 2.84 fold respectively) and lymphocytes by (36.4, 75.7, and 87.9 fold respectively). LTB4 levels were increased by 2.2, 3 and 3.2 folds respectively compared to the controls. Differential cell count from 8 day exposures demonstrated significant increase in alveolar macrophages (2.18 fold) and lymphocytes by 33.7 fold, and LTB4 levels by 8.4 folds compared to the controls. Fourteen day exposures demonstrated significant increase in alveolar macrophages (2.06 fold) and lymphocytes by 26.5 fold, and LTB4 levels by 11.8 folds as compared to the controls. 5 LO immunohistochemistry demonstrated greater intensity of 5LO in the alveolar walls and alveolar macrophages for all the treatment groups as compared to their controls. SEM study demonstrated presence of macrophages with irregular and ruffled surface in SWCNT exposed groups as compared to the controls. TEM demonstrated presence of SWCNTs in phagolysosomes, cytoplasm and vacuoles of bronchoalveolar macrophages. Chemotaxis assay on RAW macrophages and BAL macrophages showed that exogenous exposure of increasing concentration of SWCNTs with increased cell migration as compared to control cells. Such data indicate that inhaled SWCNTs induce pulmonary inflammation in hamsters with activation of 5 LO and increase in levels of LTB4.