Acute effects of inhaled urban particles and ozone - Lung morphology, macrophage activity, and plasma endothelin-1

We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m(3) for 4 hours; mass media n aerodynamic diameter, 4 to 5 mu m; Ottawa urban dust, EHC-93), followed b y 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 l ung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) r esulted in increased neutrophils and protein in lung lavage fluid. Ozone al one also decreased phagocytosis and nitric oxide production and stimulated endothelin-l secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2, Coexposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measura ble exacerbation of the ozone-related alveolar neutrophilia and permeabilit y to protein detected by lung lavage. The enhanced septal thickening was as sociated with elevated production of both macrophage inflammatory protein-2 and endothelin-l by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-l, but this re sponse was not influenced bq the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the dist ally distributed particulate dose on capillary endothelial production or fi ltration of the vasoconstrictor. Overall, equivalent patterns of effects we re 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 ma tter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects o f respirable particulate matter from ambient air appear related to paracrin e/endocrine disruption mechanisms.