Acute Effects of Inhaled Urban Particles and Ozone

Abstract

We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air appear related to paracrine/endocrine disruption mechanisms.

Air pollution: The "heart" of the problem

“…The vasopressor response was directly associated with environmental fine particle concentrations. These findings suggest that the vasoconstriction observed in the brachial artery [50] occurs in the resistance microvasculature as well, perhaps due to enhanced endothelin expression [49] and sympathetic nervous system activity [38]. We therefore speculate that chronic exposure to fine particulate air pollution, at the levels encountered in present-day industrialized nations, may be a previously unappreciated risk factor for developing essential hypertension.…”

“…Rats exposed to urban particulate matter were found to have increased circulating plasma levels of endothelin-1 [49], a marker for increased cardiovascular mortality. With these findings in mind, we investigated the effect of short-term PM 2.5 and ozone inhalation on vascular reactivity in healthy adults [50••].…”

Health Effects of Fine Particulate Air Pollution: Lines that Connect

“…284 PM exposure has also been associated with increased blood pressure in cardiac rehabilitation patients 281 and in adults with lung disease, 279 increased vasoconstriction in the pulmonary vessels of rats, 400 increased circulating levels of the vasoactive peptide endothelin in rats, 401 and elevated levels of endothelin in animals for 2 hr to up to 2 days after urban PM pollution. 402 Brook et al 250 argue that arterial vasoconstriction is a likely explanation for the PM and exercise induced ischemia (as measured by ST-Segment depression in Pekkanen et al 275 ) and enhanced cardiac ischemia in dogs exposed to concentrated PM air pollution. 379 van Eeden et al 347 note that the time course of elevated endothelin observed in animals 402 is consistent with the time course observed in recent studies of PM exposure and MI events.…”

“…402 Brook et al 250 argue that arterial vasoconstriction is a likely explanation for the PM and exercise induced ischemia (as measured by ST-Segment depression in Pekkanen et al 275 ) and enhanced cardiac ischemia in dogs exposed to concentrated PM air pollution. 379 van Eeden et al 347 note that the time course of elevated endothelin observed in animals 402 is consistent with the time course observed in recent studies of PM exposure and MI events. 259,260 Because they are so closely linked to pulmonary and systemic inflammation, mechanisms related to vasculature alterations cannot be considered independent of previously discussed COPD and inflammation/atherosclerosis-related pathways.…”

Adjuvant Activity of Ambient Particulate Matter in Macrophage Activity-Suppressed,N-Acetylcysteine-Treated, iNOS- and IL-4-Deficient Mice

“…The Ottawa dust (EHC-93) was a gift of Dr. R. Vincent (Environmental and Occupational Toxicology Division, Environmental Health Directorate, Health Canada, Ottawa, Ontario). In brief, EHC-93 contains profiles and amounts of polycyclic aromatic hydrocarbons, ions, and metals comparable to those of the standard reference materials 1648 (urban particulate matter) and 1649 (organics) of the National Institute of Standards and Technology (Gaithersburg, MD), and to a range of fine particulate materials recovered by field sampling (Bouthillier et al, 1998).…”