Multi-walled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: a 1 year post-exposure study

摘要

Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration and lactate dehydrogenase (LDH) activity and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 month, 6 months, and 1 year post-exposure. As MWCNT are often structurally compared to asbestos, a 120 μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all 3 post-exposure times. Asbestos exposure elevated LDH activity at all 3 post-exposure times and PMN infiltration at 1- and 6 months post-exposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 year post-exposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, we determined up- and down-regulated gene expression in lung tissue at 1 year post-exposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological changes similar to crocidolite asbestos, but may reach these endpoints by different mechanisms.