You are here:
Circulating factors induce coronary endothelial ceIl activation foIlowing exposure to inhaled diesel exhaust and nitrogen dioxide in humans :Evidence from a novel translational in vitro model
Citation:
Channell, M. M., M. L. Pafett, M. J. Campen, R. B. DEVLIN, AND M. C. MADDEN. Circulating factors induce coronary endothelial ceIl activation foIlowing exposure to inhaled diesel exhaust and nitrogen dioxide in humans :Evidence from a novel translational in vitro model. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 127(1):179-86, (2012).
Impact/Purpose:
These data indicate that pro-inflammatory circulating factors are elevated acutely following exposure to both diesel exhaust and a primary component thereof, NOz. These functional, translational assays offer novel approaches to assessing the cardiovascular risk associated with air pollution exposure.
Description:
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 (NOz). Plasma samples were obtained from human volunteers exposed to 100 ~g/m3 DEorfiltered airfor2hours. Asecond cohortwasexposedto 500 ppb NOz or filtered air in an identical protocol. Primary human coronary artery endothelial cells (hCAECs) were grown to confluence and treated for 24 hours with a 10% or 30% (in media) mixture of plasma obtained before, immediately post-, or 24-h post-exposure to pollutant exposures. mRNAwas isolated from hCAECs following the incubation and probed for intracellular cell adhesion molecule (ICAM-l) and vascular cell adhesion molecule (VCAM-l)expression. ICAM-lmRNAexpression wasincreasedbyplasmaobtained atboth timepoints following the NOz exposures. VCAM-lwas significantly elevated in cells treated with plasma obtained 24-h following diesel exposure, and at both timepoints following NOz exposure. IL-8 protein was elevated in the hCAEC supernatant when cells were incubated with plasma from NOz exposures. These data indicate that pro-inflammatory circulating factors are elevated acutely following exposure to both diesel exhaust and a primary component thereof, NOz. These functional, translational assays offer novel approaches to assessing the cardiovascular risk associated with air pollution exposure.
