Abstract
BackgroundMulti-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis.MethodsMWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA.ResultsMice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung.ConclusionsThese results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures.
Highlights
Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties
Ryman-Rassmusen et al demonstrated that mice exposed to MWCNT following ovalbumin sensitization developed significantly increased airway fibrosis and lung inflammation compared to mice that were not treated with MWCNTs but challenged with ovalbumin [7]
Instillation of MWCNTs in C57BL/6 Mice Elicits DoseDependent Changes in Pulmonary Function To determine if MWCNT exposure elicits any physiologically relevant toxicity, we examined pulmonary function in C57BL/6 mice following instillation of vehicle, 1, 2, or 4 mg/kg of MWCNTs
Summary
Animals Male C57BL/6 mice were obtained from Jackson Laboratories (Bar Harbor, ME, USA) at 9 to 10 weeks of age. Following pulmonary function measurements mice were euthanized for bronchoalveolar lavage and collection of lung tissue. BAL and cell differential counts After measuring pulmonary function parameters, the right lung of each mouse was lavaged in situ four times with a specific volume (26.25 mL/kg body weight) of ice-cold Hanks balanced salt solution (HBSS). Mouse fibrosis PCR-array Total RNA from left lung tissue of additional mice was isolated using a Qiagen RNeasy Mini Kit (Qiagen, Valencia, CA, USA) according to the manufacturer’s recommendations. Total RNA (2.5 μg) was reverse-transcribed to cDNA using SABiosciences’s RT2 First Strand Kit (Qiagen, Frederick, MD, USA) and applied to Mouse Fibrosis PCR Arrays (Cat.# PAMM-120; 96-well format) following SABiosciences recommendations. Differences were considered statistically significant at p < 0.05
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