1. Prolonged systemic inflammation and damage to the vascular endothelium following intratracheal instillation of air pollution nanoparticles in rats.
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Rachel A Adams* , Halima Al-Bulushi*, Ameena Al-Mosawi*, Omolade Alabi*, Jenni Hawke*, Paul Foley*, Sally J Hicks*, Stephen Potter*, Kelly Bérubé†, Tim Jones‡ and Shelley-Ann Evans*.
Cardiff School of Health Sciences, UWIC, Western Avenue, Cardiff CF5 2YB, UK.
† School of Biosciences, Cardiff University, Museum Avenue, PO Box 911, Cardiff CF10 3US, UK
‡School of Earth and Ocean Sciences, Cardiff University, Park Place, Cardiff, CF10 3YE,UK.
Introduction
Exposure to particulate air pollution is associated with an increased cardiovascular risk but the mechanisms involved are poorly understood1,2. Inflammatory changes to leucocytes and damage to the vascular endothelium are known to be predictors of cardiovascular disease. Damage to the vascular endothelium is associated with an increase in blood von Willebrand factor (vWF) and sICAM-1, which are secreted from the vascular endothelium, and increases in these markers are independent risk factors for cardiovascular disease. The aim of this study was to assess the effect, in rats, of intratracheal instillation of particulate air pollution (PM10) on leucocyte activation and damage to the vascular endothelium.
Methods
Rats were exposed to air pollution nanoparticles by intratracheal instillation, with blood collected 3 days and 6 weeks after dust instillation. Blood was collected into EDTA (1.5mg/ml). Intracellular F-actin content was determined by labelling with FITC-phalloidin. Mean fluorescence intensity (MFI) was then measured by flow cytometry and cells were visualised by fluorescence microscopy. Plasma neutrophil elastase, vWF and sICAM-1 were determined by ELISA. All results are expressed as mean ±SEM (n=10 for control group and n= 15 for test group), and all statistical analyses were performed using Minitab.
Results
In rats exposed to air pollution nanoparticles :
There was a significant decrease in monocyte cell count and a significant increase in monocyte F actin content. (table 1).
There was a significant increase in the two markers of endothelial cell damage, vWF (fig. 2) and sICAM-1 (fig. 3)
There was a significant increase in plasma neutrophil elastase (fig. 4)
control
3 days post
6 weeks post P
Monocytes (x 109/L)
0.193±0.008
0.150±0.008
0.149±0.009
0.003
Monocyte F-actin (MFI)
403±41
606±67
484±38
0.004
Table 1. The effects of instillation of particles on monocyte count and monocyte intracellular F-actin concentration (MFI).
Figure 4. The effect of intratracheal instillation of nanoparticles on plasma concentration of neutrophil elastase. P= 0.06.
Figure 3. The effect of intratracheal instillation of nanoparticles on plasma concentration of soluble ICAM-1. P=
Figure 1. Visualised intracellular F-actin in typical blood monocyte and platelets.
Figure 2. The effect of intratracheal instillation of nanoparticles on plasma concentration of von Willebrand factor. P=0.006.
Conclusions
Lung exposure to particulate air pollution causes systemic inflammation, and the observed changes persist long after the initial instillation event.
Lung exposure to particulate air pollution causes activation of leucocytes, shown by increased F-actin in monocytes, which increases cell rigidity and hence decreases cell deformability, which can result in trapping of cells in the microcirculation.
Activated leucocytes also cause the increased levels of plasma neutrophil elastase observed here, which activate and damage the vascular endothelium causing increased shedding of vWF and sICAM-1 into the plasma.
Activation of leucocytes and the endothelium results in increased adhesion and trapping of leucocytes, seen here as a decrease in the number monocytes in the circulation. Movement of monocytes into the arterial wall is associated with atherosclerosis and the inflammatory changes described here could be, in part, the mechanism by which air pollution increases the incidence of cardiovascular disease.
Exposure to even short term episodes of high levels of particulate air pollution could cause significant systemic inflammatory changes which increase the risk of developing cardiovascular disease and complications.
References
Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, Luepker R, Mittleman M, Samet J, Smith SC, Jr., and Tager I. Air (2004) Pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 109:
Evans SA, Al-Mosawi A, Adams RA, and Berube KA. Inflammation, edema, and peripheral blood changes in lung-compromised rats after instillation with combustion-derived and manufactured nanoparticles. Experimental lung research 32: , 2006.