Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, PC183

Poster Communications

Prolonged systemic inflammation and damage to the vascular endothelium following intratracheal instillation of air pollution nanoparticles in rats

R. A. Adams1, H. Al-Bulushi1, A. Al-Mosawi1, O. Alabi1, J. Hawke1, P. Foley1, S. Hicks1, S. Potter1, K. Berube2, T. Jones3, S. Evans1

1. Cardiff School of Health Sciences, UWIC, Cardiff, United Kingdom. 2. Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom. 3. Cardiff School of Earth and Ocean Sciences, Cardiff University, Cardiff, United Kingdom.

Exposure to particulate air pollution is associated with an increased cardiovascular risk but the mechanisms involved are poorly understood.[1] Increased inflammation and endothelial damage are associated with cardiovascular disease.[2] The aim of this investigation was to assess the effect, in rats, of intratracheal instillation of particulate air pollution on leucocyte activation and damage to the vascular endothelium. The rats were lightly anaesthetised with halothane before receiving intratracheal instillations. They were then exposed to particulate air pollution by intratracheal instillation of PM10 (ambient air pollution particles of diameter less than 10μm suspended in 0.15 M saline at a concentration of 1 mg particles per ml). Blood was collected from controls (n=10) and 3 days (n=15) and 6 weeks (n=15) post instillation. Partial differential leucocyte counts were performed. Intracellular F-actin content of blood PMNs and monocytes was determined by staining with FITC-phalloidin and flow cytometry (MFI). Plasma neutrophil elastase, von Willebrand factor (vWF) and sICAM-1 were determined by ELISA. There was a significant increase in monocyte F-actin from 403±41(mean MFI±SEM) in controls to 606±67 at 3 days post instillation and 484±38 6 days post instillation (p=0.004, ANOVA) and a decrease in monocyte cell count from 0.193±0.008x106cells/ml in controls to 0.150±0.008x106cells/ml at 3 days post and 0.149±0.009x106cells/ml at 6 weeks post(p=0.003, ANOVA). There were no significant changes in PMN MFI (p=0.369, ANOVA) or cell counts (p=0.753, ANOVA). Plasma neutrophil elastase increased from 175±44 ng/ml in controls to 288±26 ng/ml 3 days post instillation (p=0.038). There was an increase in two markers of endothelial damage. vWF increased from 0.160±0.015 IU/ml in controls to 0.224±0.015 IU/ml at 3 days post and 0.208±0.01 IU/ml at 6 weeks post (p=0.006, ANOVA). sICAM-1 increased from 17.75±0.70 ng/ml in controls to 19.03±0.33 ng/ml at 3 days post and 21.72±1.16 ng/ml at 6 weeks post (p=0.009, ANOVA). We conclude that lung exposure to particulate air pollution causes systemic inflammation. Inflammation leads to activation of blood leucocytes which increases assembly of the cytoskeleton and decreased cell deformation during flow. Activated cells produce proteolytic enzymes which activate and damage the endothelium causing increased adhesion molecule expression. Activation of leukocytes and the endothelium results in increased adhesion and trapping of leucocytes which is recorded as a decrease in monocytes in the bulk circulation. Movement of monocytes into the arterial wall is associated with atherosclerosis and the inflammatory changes described here could be the mechanism by which air pollution increases cardiovascular disease. The inflammatory changes observed persist long after the initial instillation event. Exposure to even short term episodes of high levels of particulate air pollution could cause systemic inflammatory changes which increase the risk of developing cardiovascular risk.

Where applicable, experiments conform with Society ethical requirements