Circulating Factors Induce Coronary Endothelial Cell Activation Following Exposure to Inhaled Diesel Exhaust and Nitrogen Dioxide in Humans: Evidence From a Novel Translational In Vitro Model

Abstract

The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen dioxide (NO(2)). Plasma samples were obtained from human volunteers exposed to 100 μg/m(3) DE or filtered air for 2 h. A second cohort was exposed to 500 ppb NO(2) or filtered air in an identical protocol. Primary human coronary artery endothelial cells (hCAECs) were grown to confluence and treated for 24 h with a 10 or 30% (in media) mixture of plasma obtained before, immediately post or 24 h postexposure to pollutant exposures. Messenger RNA (mRNA) was isolated from hCAECs following the incubation and probed for intracellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) expression. ICAM-1 mRNA expression was increased by plasma obtained at both timepoints following the NO(2) exposures. VCAM-1 was significantly elevated in cells treated with plasma obtained 24 h following diesel exposure and at both timepoints following NO(2) exposure. Interleukin-8 protein was elevated in the hCAEC supernatant when cells were incubated with plasma from NO(2) exposures. These data indicate that proinflammatory circulating factors are elevated acutely following exposure to both DE and a primary component thereof, NO(2). These functional translational assays offer novel approaches to assessing the cardiovascular risk associated with air pollution exposure.

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…Dose-related endothelial and inflammatory responses were also found in the range 2.6-10.6 ppm. Channell et al (2012) found that plasma from healthy adults exposed to 0.5 ppm NO 2 for 2 hours was able to activate cultured primary human coronary endothelial cells. This suggested that a circulating factor was mediating, at least in part, the endothelial response that may underly the cardiovascular epidemiological findings.…”

“…A study in mice suggested that effects in the lung due to 20 ppm NO 2 for 10 days are worse with a small increase in vitamin C dose than with a large increase (Zhang et al, 2010), perhaps due to vitamin C increasing NO 2 absorption into the epithelial lining fluid (Enami, Hoffmann & Colussi, 2009). All these concentrations (apart from Channell et al, 2012) are far in excess of the ambient concentrations linked to health effects in population studies, and the studies are not designed to show whether the mechanisms extend down to lower concentrations -that is, the mechanisms may or may not be relevant.…”

Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood–brain barrier impairment

“…We used cultured mouse cerebrovascular endothelial cells (mCECs) as biosensors of cumulative inflammatory mediators in serum from MWCNT-exposed mice, an approach that has proven valuable in toxicologic and clinical applications (16,28). Microarray analysis was performed on mRNA isolated from primary mCECs following incubation with serum collected from MWCNT-or DM-exposed mice (at 4 h postexposure) at 10% in medium for 4 h (Fig.…”

“…Despite their very limited ability to translocate beyond the lung (12), MWCNTs have been shown to induce extrapulmonary toxicity through as-yet unknown pathways (13)(14)(15). Pulmonary interactions with inhaled pollutants, including MWCNTs, can generate secondary bioactive factors that spill over into the systemic circulation and are distributed throughout the body (15)(16)(17). One consequence of these circulating factors is activation of the endothelium, characterized by the expression of adhesion molecules and recruitment/activation of circulating inflammatory cells (18).…”

PM, Carbon, PAH, and Particle-Extract-Induced Cytotoxicity of Emissions from a Diesel Generator Fueled with Waste-Edible-Oil-Biodiesel

“…The DEP-bound PAHs include high molecular weight PAHs with more carcinogenic potency (such as BaA, CHR, BbF, BaP, and IND) (Kerminen et al, 1997;Soontjens et al, 1997). Therefore, the exposure to the emission environment of diesel engines increases the risk of the occurrence of cardiovascular diseases, respiratory diseases, and lung cancer that negatively affect human health (Sultan, 2007;Channell et al, 2012).…”