The effect of air pollution particles on leucocyte function and cardiovascular disease
Al Bulushi, Halima
Cardiff Metropolitan University
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In epidemiological studies in humans, increased exposure to airborne particulate matter is associated with increases in cardiovascular malfunction, hospital admissions and morbidity and mortality rates. Although different reasons have been postulated to link inflammatory changes induced by particle inhalation to such cardiovascular alterations, the causative mechanisms of the cardiovascular insult are, as yet, uncertain. An understanding of the mechanisms involved offers the potential for intervention to reduce the risks. In this study, the hypothesis that air pollution-derived nano-particles cause cardiovascular problems by causing inflammatory activation of leucocytes, which can subsequently lead to damage of the vascular endothelium, was tested. Leucocyte activation was assessed by measurement of changes in the levels of intracellular F-actin, and by measurement of release of neutrophil elastase. Damage to the vascular endothelium was assessed by measurement of vonWillebrand factor. The results show that instillation of particles into the lung is associated with inflammatory changes in the systemic circulation. Instillation caused activation of leucocytes which release the proteolytic enzyme neutrophil elastase. Increased elastase secretion is possibally (as the results were not statistically significant) associated with activation and damage to the vascular endothelium which was recorded as an increase in plasm von Willebrand factor concentration after short term exposure to the particles i.e. three days. Activation of the endothelium resulted in increased expression of the adhesion molecule sICAM-1 which is shed into the plasma and causes an increase in the measured plasma soluble sICAM-1 concentration only at six weeks post instillation i.e. long term exposure. This study also showed that the particles clearly induce F--actin polymerization and cause activation of leucocytes; the higher the particle concentration the greater the biological effect on the leucocytes. Also, the longer the particle stays in the blood the greater the biological effect on the cells. The particles clearly enter cells as they were visualized inside cells during microscopic examination. Taken together, visual evidence of the intracellular location of particles, and flow cytometric determination of increase cytoskeletal assembly, support the hypothesis that air pollution particles may enter leucocytes by phagocytosis. Although carbon black has often been suggested as a negative (non-toxic) control, in high concentrations it can cause adverse effects to the leucocytes. This study also confirms the toxicity of diesel exhaust particles on the cells as it can cause cell death. Taken together all the evidence in this study suggests that leucocytes phagocytose particles and then extravasate into the tissues resulting in translocation of particles to tissues distant from the site of exposure. The inflammatory changes observed here persist long after the initial instillation event and exposure to even short episodes of air pollution could be associated with long term increases in cardiovascular risk.
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