Journal Article

Circulating Factors Induce Coronary Endothelial Cell Activation Following Exposure to Inhaled Diesel Exhaust and Nitrogen Dioxide in Humans: Evidence From a Novel Translational <i>In V</i><i>itro</i> Model

Meghan M. Channell, Michael L. Paffett, Robert B. Devlin, Michael C. Madden and Matthew J. Campen

in Toxicological Sciences

Volume 127, issue 1, pages 179-186
Published in print May 2012 | ISSN: 1096-6080
Published online February 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs084
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

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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 (NO2). Plasma samples were obtained from human volunteers exposed to 100 μg/m3 DE or filtered air for 2 h. A second cohort was exposed to 500 ppb NO2 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 NO2 exposures. VCAM-1 was significantly elevated in cells treated with plasma obtained 24 h following diesel exposure and at both timepoints following NO2 exposure. Interleukin-8 protein was elevated in the hCAEC supernatant when cells were incubated with plasma from NO2 exposures. These data indicate that proinflammatory circulating factors are elevated acutely following exposure to both DE and a primary component thereof, NO2. These functional translational assays offer novel approaches to assessing the cardiovascular risk associated with air pollution exposure.

Keywords: diesel; nitrogen dioxide; cardiovascular; air pollution; endothelial activation; ICAM-1; VCAM-1; translational; interleukin-8

Journal Article.  4644 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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