SYSTEMIC EFFECT OF PARTICULATE AIR POLLUTION

Abstract

The association in epidemiological studies between particulate air pollution (PM10) and increased mortality and morbidity from cardiovascular disease is well established. However, the mechanism(s) by which PM10 produces these effects is unknown. Wehave developed a hypothesis that ultrafine components of PM10 cause lung inflammation by creating local lung oxidative stress, which activates transcription factors such as NF-kappaB and hence the transcription of genes for inflammatory mediators. In a series of studies in vivo in the rat and using cultured airspace epithelial cells in vitro, we have tested this hypothesis using environmental PM10 and fine (CB 260 nm in diameter) and ultrafine (UfCB, 14 nm in diameter) carbon particles, since carbon is a major component of PM10. Wehave shown that compared with CB, which produces trivial effects, UFCB and PM10 produce local lung inflammation, increased epithelial permeability,and evidence of oxidative stress. Wehave also shown that PM10 also activates NF-kappaB in airspace epithelial cells. Wealso hypothesized that the local lung inflammation produced by PM10 may result in systemic effects, in particular systemic oxidative stress and enhanced blood coagulation, which may have a role in the adverse cardiovascular effects induced by PM10. To test this hypothesis we measured oxidative stress and changes in coagulation factors in plasma following the inhalation of UFCB, CB, or instillation of PM10 in the rat. Immediately after 7 h inhalation of UFCB (1000 (g/m3) there was a significant decrease in the antioxidant capacity in rat plasma, which fell further 16 and 48 h after cessation of the inhalation. A similar fall in plasma antioxidant capacity was shown 6 h after instillation of PM10 (125 mug). In contrast, there were no significant changes in antioxidant capacity in rats after 7 h of inhalation of CB at similar concentrations. The levels of factor VII in plasma, which is a key factor in the intrinsic pathway of coagulation cascade, increased at time points from 6 h to 7 days after inhalation of UFCB, but did not change after CB exposure. There were no changes in plasma fibrinogen or other coagulation factors after inhalation of particles. Thus, inhalation of ultrafine carbon black particles and instillation of PM10 in rats decreases plasma antioxidant capacity as an indication of systemic oxidative stress. Ultrafine carbon black particles also cause increased factor VII levels in the plasma, a known risk factor for adverse cardiovascular events. These studies help to explain the relationship between the levels of particulate air pollutants and cardiovascular morbidity/mortality.