Manufactured and airborne nanoparticle cardiopulmonary interactions: a review of mechanisms and the possible contribution of mast cells

Abstract

Human inhalation exposures to manufactured nanoparticles (NP) and airborne ultrafine particles (UFP) continues to increase in both occupational and environmental settings. UFP exposures have been associated with increased cardiovascular mortality and morbidity, while ongoing research supports adverse systemic and cardiovascular health effects after NP exposures. Adverse cardiovascular health effects include alterations in heart rate variability, hypertension, thrombosis, arrhythmias, increased myocardial infarction, and atherosclerosis. Exactly how UFP and NP cause these negative cardiovascular effects is poorly understood, however a variety of mediators and mechanisms have been proposed. UFP and NP, as well as their soluble components, are known to systemically translocate from the lung. Translocated particles could mediate cardiovascular toxicity through direct interactions with the vasculature, blood, and heart. Recent study suggests that sensory nerve stimulation within the lung may also contribute to UFP- and NP-induced acute cardiovascular alterations. Activation of sensory nerves, such as C-fibers, within the lung may result in altered cardiac rhythm and function. Lastly, release of pulmonary-derived mediators into systemic circulation has been proposed to facilitate cardiovascular effects. In general, these proposed pulmonary-derived mediators include pro-inflammatory cytokines, oxidatively-modified macromolecules, vasoactive proteins, and prothrombotic factors. These pulmonary-derived mediators have been postulated to contribute to the subsequent prothrombotic, atherogenic, and inflammatory effects after exposure. This review will evaluate the potential contribution of individual mediators and mechanisms in facilitating cardiopulmonary toxicity following inhalation of UFP and NP. Lastly we will appraise the literature and propose a hypothesis regarding the possible role of mast cells in contributing to these systemic effects.

Influence of physicochemical properties of silver nanoparticles on mast cell activation and degranulation

“…Even though mast cells appear to be central in the pathogenesis following NP exposure little research has been done assessing the direct interaction of NPs with mast cells. While mast cells are well-known to be involved in allergic conditions, it is currently unclear if NPs have the capacity to induce and/or promote an allergic disease state (Podila and Brown, 2013; Shannahan and Brown, 2014; Shannahan et al, 2012). One study reported that AgNPs can induce mast degranulation in the RBL-2H3 rat basophilic cell line, however, the study was focused on real-time live cell imaging of the degranulation process but not the influence of physicochemical properties of AgNPs (Yang et al, 2010).…”

Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling

“…[8][9][10][11] It has been confirmed that NPs can systemically translocate to the circulation from the lung. 12 Subsequently, translocated particles could mediate cardiovascular effects through direct interaction with vasculature, blood, and the heart. The cardiovascular toxicity of NPs has gradually drawn attention.…”

Immunotoxicological impact of engineered nanomaterial exposure: mechanisms of immune cell modulation

“…In our lab, we have demonstrated that exposure to MWCNTs by oropharyngeal aspiration in C57BL/6 mice induced a significant increase in production of IL-33 (Wang et al, 2011). We speculated that the increased levels of IL-33, released from damaged lung epithelial cells, subsequently activated mast cells resulting in adverse pulmonary and cardiovascular responses in mice (Shannahan et al, 2012). These MWCNT induced toxicities appear to be mast cell dependent as MWCNT failed to induce these toxicities in mast cell-deficient mice.…”