Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity.

Pathology/Physiology Research Branch, HELD, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 4.11). 06/2008; 38(5):579-90. DOI: 10.1165/rcmb.2007-0255OC
Source: PubMed

ABSTRACT Carbon nanotubes (CNT), with their applications in industry and medicine, may lead to new risks to human health. CNT induce a robust pulmonary inflammation and oxidative stress in rodents. Realistic exposures to CNT may occur in conjunction with other pathogenic impacts (microbial infections) and trigger enhanced responses. We evaluated interactions between pharyngeal aspiration of single-walled CNT (SWCNT) and bacterial pulmonary infection of C57BL/6 mice with Listeria monocytogenes (LM). Mice were given SWCNT (0, 10, and 40 mug/mouse) and 3 days later were exposed to LM (10(3) bacteria/mouse). Sequential exposure to SWCNT/LM amplified lung inflammation and collagen formation. Despite this robust inflammatory response, SWCNT pre-exposure significantly decreased the pulmonary clearance of LM-exposed mice measured 3 to 7 days after microbial infection versus PBS/LM-treated mice. Decreased bacterial clearance in SWCNT-pre-exposed mice was associated with decreased phagocytosis of bacteria by macrophages and a decrease in nitric oxide production by these phagocytes. Pre-incubation of naïve alveolar macrophages with SWCNT in vitro also resulted in decreased nitric oxide generation and suppressed phagocytizing activity toward LM. Failure of SWCNT-exposed mice to clear LM led to a continued elevation in nearly all major chemokines and acute phase cytokines into the later course of infection. In SWCNT/LM-exposed mice, bronchoalveolar lavage neutrophils, alveolar macrophages, and lymphocytes, as well as lactate dehydrogenase level, were increased compared with mice exposed to SWCNT or LM alone. In conclusion, enhanced acute inflammation and pulmonary injury with delayed bacterial clearance after SWCNT exposure may lead to increased susceptibility to lung infection in exposed populations.

Download full-text


Available from: Vincent Castranova, Jul 09, 2015
  • Source
    • "Witasp et al. (2009) reported that SWCNTs could impair the phagocytic function of human macrophages at non-cytotoxic concentration, leading to inhibited elimination of apoptotic cell corpses. Decreased phagocytosis might also result in decreased bacterial clearance and enhanced pulmonary inflammation and infectivity, in vivo (Shvedova et al. 2008). Similar to this study, AF-SWCNTs and SWCNTs, at non-cytotoxic concentrations , affected the phagocytic ability of mouse primary peritoneal macrophages (Figure 5). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract It is increasingly important to understand the single-walled carbon nanotubes' (SWCNTs) immune response as their increasingly biomedical researches and applications. Macrophages and T cells play important roles in scavenging foreign materials and pathogens and regulating immune response. In this work, primarily cultured murine peritoneal macrophages and purified splenic T cells were utilised to determine the toxic effects of SWCNTs and acid-functionalised SWCNTs (AF-SWCNTs) on the immune system, especially on macrophage functions. Macrophages were exposed to 0-50 μg/ml of CNTs for 24 h and no significant cytotoxicity was found by live/dead and annexin-V-FITC/PI analyses. The TEM images revealed that AF-SWCNTs were engulfed mostly through phagocytosis and located in lysosomes of macrophages. Measurement of mitochondrial membrane potential and proteasome subunit gene expression demonstrated that 10 and 50 μg/ml AF-SWCNTs could damage mitochondrial function and proteasome formation in a concentration-dependent manner. Functional analyses revealed that the percentage of phagocytic cells were affected significantly by 20 μg/ml CNTs, and 5 μg/ml AF-SWCNTs inhibited the phagocytic efficiency of latex beads in macrophages. The accessory cell function was affected by both AF-SWCNTs and SWCNTs at concentrations of 10 and 50 μg/ml, respectively. Furthermore, AF-SWCNT biased naïve T-cell differentiation to Th1 type by inducing the production of IFN-γ and TNF, implying the potential risk of Th1-associated diseases (e.g. autoimmune diseases and inflammation) on AF-SWCNT exposure.
    Nanotoxicology 05/2012; DOI:10.3109/17435390.2012.694487 · 7.34 Impact Factor
  • Source
    • "Higher lung levels of MCP-1 were also found after exposure to carbon NPs (Inoue et al., 2005). Similar cytokines/chemokines elevations in BAL fluid were found in case of pharyngeal aspiration with single wall carbon nanotubes (SWCNT) 3 days post exposure (Shvedova et al., 2008). Interestingly , even though augmentation of IL-12 (p40) cytokine that is known to be elevated with profibrogenic exposures was observed in Cu-exposed animals, no fibrotic changes in the lung tissues were found in mice necropsied immediately or three weeks post exposure (Pettibone, et al., 2008). "
    General, Applied and Systems Toxicology, 09/2011; , ISBN: 9780470744307
  • Source
    • "Adult rats exposed to the same exposure conditions as younger animals did not show any significant changes in the expression of the airway neurotrophins NGF and BDNF or their receptors, TrKa, p75, and TrKb. These age-related differences have already been shown to play a critical role in determining the susceptibility of the developing airways to other inhaled pathogens (Piedimonte, 2001; Hu et al., 2002; Piedimonte et al., 2004), and, although the magnitude of the particle-induced airway responses in our study was not as dramatic as with more toxic inhalants, data suggest the possibility that this type of environmental exposure may render the lung more sensitive to secondary insults present in the environment, including respiratory viruses (Lambert et al., 2003; Mossman et al., 2007; Shvedova et al., 2008). The disruption of neurotrophin-related airway responses was associated to AHR as demonstrated by the presence of a higher baseline specific airway resistance in exposed animals compared to their age-matched controls and by the enhanced response to methacholine challenge in treated animals 1 h after the last exposure. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Exposure to ambient nanoparticles (defined as particulate matter [PM] having one dimension <100 nm) is associated with increased risk of childhood and adult asthma. Nanomaterials feature a smaller aerodynamic diameter and a higher surface area per unit mass ratio compared to fine or coarse-sized particles, resulting in greater lung deposition efficiency and an increased potential for biological interaction. The neurotrophins nerve growth factor and brain-derived neurotrophic factor are key regulatory elements of neuronal development and responsiveness of airway sensory neurons. Changes in their expression are associated with bronchoconstriction, airway hyperresponsiveness, and airway inflammation. The neurogenic-mediated control of airway responses is a key pathophysiological mechanism of childhood asthma. However, the effects of nanoparticle exposure on neurotrophin-driven airway responses and their potential role as a predisposing factor for developing asthma have not been clearly elucidated. In this study, in vivo inhalation exposure to titanium dioxide nanoparticles (12 mg/m(3); 5.6 h/d for 3 d) produced upregulation of lung neurotrophins in weanling (2-wk-old) and newborn (2-d-old) rats but not in adult (12-wk-old) animals compared to controls. This effect was associated with increased airway responsiveness and upregulation of growth-related oncogene/keratine-derived chemokine (GRO/KC; CXCL1, rat equivalent of human interleukin [IL]-8) in bronchoalveolar lavage fluid. These data show for the first time that exposure to nanoparticulate upregulates the expression of lung neurotrophins in an age-dependent fashion and that this effect is associated with airway hyperresponsiveness and inflammation. These results suggest the presence of a critical window of vulnerability in earlier stages of lung development, which may lead to a higher risk of developing asthma.
    Journal of Toxicology and Environmental Health Part A 08/2010; 73(20):1353-69. DOI:10.1080/15287394.2010.497436 · 1.83 Impact Factor