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We have demonstrated that intratracheal instillation of 0.5 mg of single-walled carbon nanotubes into male ICR mice induced alveolar macrophage activation, various chronic inflammatory responses, and severe pulmonary granuloma formation

Single-walled carbon nanotubes can induce pulmonary injury in mouse model.

NANO LETTERS, no. 2 (2008): 437-445

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摘要

Carbon nanotubes are a nanomaterial that is extensively used in industry. The potential health risk of chronic carbon nanotubes exposure has been raised as of great public concern. In the present study, we have demonstrated that intratracheal instillation of 0.5 mg of single-walled carbon nanotubes (SWCNT) into male ICR mice (8 weeks old)...更多

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简介
  • Carbon nanotubes are a nanomaterial that is extensively used in industry. The potential health risk of chronic carbon nanotubes exposure has been raised as of great public concern.
  • This is consistent with the experimental results reported in the earlier literature.[22,23] The granulomas are mainly composed of aggregates of macrophages laden with SWCNT particles, and thereof an investigation of the genome-wide gene expression changes in macrophages exposed to SWCNT, associated with a detailed signaling pathway analysis, ought to provide molecular insights into this type of granuloma formation.
重点内容
  • Carbon nanotubes are a nanomaterial that is extensively used in industry
  • The granulomas are mainly composed of aggregates of macrophages laden with single-walled carbon nanotubes (SWCNT) particles, and thereof an investigation of the genome-wide gene expression changes in macrophages exposed to SWCNT, associated with a detailed signaling pathway analysis, ought to provide molecular insights into this type of granuloma formation
  • SWCNT particles possess fibrous structure with diameters about 1∼2 nm and lengths ranging from tens of nanometers to several micrometers
  • The aforementioned experimental evidence reasonably suggest that the SWCNTrelated cytotoxicity could be attributed to the geometry and surface chemistries of them.[12,13,21]
  • We used a nontoxic dispersion surfactant, Pluronic F-68, as the experimental controls in our in vitro and in vivo studies to differentiate the true cytotoxic mechanisms mediated by SWCNT particles themselves
  • This study shows that the SWCNT challenge endows macrophages with an antigen-presenting function by increasing the expression level of HLA-DR, CD80, and CD40, which are able to interact with T cell receptor (TCR), CD28, and CD40L, respectively, on T cells resulting in T cell activation and proliferation
结果
  • To elucidate the SWCNT-induced cytotoxicity at the molecular level, the authors measured the gene expression changes in human THP-1 derived macrophages exposed to SWCNT for 24 h using Affymatrix microarrays.
  • The network suggests that the uptake of SWCNT into macrophages is able to activate nuclear factor κB (NF-κB) and activator protein 1 (AP-1), and this leads to oxidative stress, the release of proinflammatory cytokines, the recruitment of leukocytes, an induction of protective and antiapoptotic gene expressions, and the activation of T cells.
  • The interaction of CD28 and CD40L on the T lymphocyte with the B7 (CD80 or CD86) and CD40 proteins, respectively, on the APC provides the necessary costimulatory second signal.[38,39] The present study showed that SWCNT exposure to macrophages induced significant expression of the lymphocyte-adhesive molecule ICAM-1, the T cell migration chemokine IP-10, and the MHC class II HLA-DRA molecule, which can associate with its costimulatory molecules, CD40 and CD80 (Figure 2 and Table 2).
  • SWCNT particles reveal more profound cytotoxicity than non-carbon nanoparticles such as quartz (SiO2).[13,21] Collectively, the aforementioned experimental evidence reasonably suggest that the SWCNTrelated cytotoxicity could be attributed to the geometry and surface chemistries of them.[12,13,21] The present study is focused not on discovering what physical or chemical properties of SWCNT particles induce cytotoxicity in cells or animals exposed to them, but on exploring how SWCNT particles regulate cellular cytotoxicity at a molecular level.
结论
  • By comparing the gene expression changes of the various antioxidative enzyme system such as SOD2, catalase, and glutathione peroxidase in macrophages under SWCNT treatment, the activity of these radical scavenging enzymes seems to be impaired as a result of the increase in local oxidative stress associated with H2O2 accumulation.
  • This study shows that the SWCNT challenge endows macrophages with an antigen-presenting function by increasing the expression level of HLA-DR, CD80, and CD40, which are able to interact with TCRs, CD28, and CD40L, respectively, on T cells resulting in T cell activation and proliferation.
表格
  • Table1: Potentially Affected Pathways Selected by the Pathway Scoring Methoda p-value pathway title website
  • Table2: Quantitative Real-Time PCR Primer Sequences and Measurements Expressed as Fold Increase Relative to the Control SWCNT Untreated Macrophages ( Standard Deviation (SD) from Two Experiments for the Genes Involving in SWCNT Associated Cytotoxicity accession number gene symbol forward primer reverse primer average fold change
Download tables as Excel
基金
  • This work was supported by a grant from National Science Council, Taiwan (NSC95-2312-B194-003). Supporting Information Available: A detailed description of the experimental procedures, pathway scoring computation method, and gene expression and related information involved in the potentially affected pathways listed in Table 1
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