Impaired Clearance and Enhanced Pulmonary Inflammatory/Fibrotic Response to Carbon Nanotubes in Myeloperoxidase-Deficient Mice

Abstract

Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo . Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results provide direct evidence for the participation of MPO – one of the key-orchestrators of inflammatory response – in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterials through genetic or pharmacological manipulations.

Dual Acute Proinflammatory and Antifibrotic Pulmonary Effects of Short Palate, Lung, and Nasal Epithelium Clone–1 after Exposure to Carbon Nanotubes

“…Although SWCNTs are versatile and beneficial in various applications, the inhalation of these nanoparticles exerts negative effects on the normal physiological functions of lungs, and causes pulmonary toxicity (2)(3)(4)(5). We previously demonstrated that the pharyngeal aspiration of SWCNTs elicits pulmonary effects in C57BL/6 mice, with a combination of robust, acute inflammation and early-onset yet progressive fibrosis and granulomas (2,5,6). The early phase of lung innate immune responses to SWCNTs is characterized by inflammation mediated by phagocytic cells, namely, polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs) (7).…”

Genotoxicity of nanomaterials in vitro: treasure or trash?

“…Interestingly, at least for multi-walled CNTs, most of the ROS formation seems to result from cellular activation and an involvement of NADPH oxidase and superoxide radicals (Funahashi et al 2015). This is contrasting the results obtained with asbestos fibers, as do data that provide evidence that CNT fibers may also scavenging ROS to certain extents, an effect that actually should be inversely related to its genotoxicity (van Berlo et al 2012). Although these effects are currently not fully understood, the assumption that the mechanisms of CNTand asbestos-mediated toxicity might be similar reveals rather premature.…”

“…For carbon-based materials, most work is focused on carbon nanotubes (CNTs), where plenty of studies have demonstrated a genotoxic potential for both single-and multi-walled CNTs (reviewed in van Berlo et al 2012). Mechanisms of genotoxicity were often linked to oxidative stress, yet formation of reactive oxygen species (ROS) in cells might also be protective in the case of CNTs due to oxidative biodegradation (Shvedova et al 2012).…”

“…Mechanisms of genotoxicity were often linked to oxidative stress, yet formation of reactive oxygen species (ROS) in cells might also be protective in the case of CNTs due to oxidative biodegradation (Shvedova et al 2012). In principle, ROS can be directly CNT-induced in the vicinity of cells (e.g., neutrophils), or may arise upon cellular internalization through the interference of CNTs with mitochondrial respiration or via depletion of antioxidant species (reviewed in Manke et al 2013).…”

Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution

“…99 An in vivo study on MPO-deficient mice revealed that as a result of lower oxidation, the inflammatory response to SWNTs was higher than in the wild-type mouse, which led to a lower clearance rate. 102 Other phagocytic cells, such as brain microglia, have also demonstrated partial biodegradation of MWNTs after 14 days of in vivo stereotactic administration into the mouse motor cortex. 103 The partially degraded CNT could yet be a cause for concern not only due to its long-term proinflammatory potential, but also because of the molecular byproducts of the degradation pathway, such as polyaromatic hydrocarbons.…”