Oxidative interactions of synthetic lung epithelial lining fluid with metal-containing particulate matter

Epidemiology studies show association of morbidity and mortality with expos ure to ambient air particulate matter (PM). Metals present in PM may cataly ze oxidation of important lipids and proteins present in the lining of the respiratory tract. The present study investigated the PM-induced oxidation of human bronchoalveolar lavage (BAL) fluid (BALF) and synthetic lung epith elial lining fluid (sELF) through the measurement of oxygen incorporation a nd antioxidant depletion assays. Residual oil fly ash (ROFA), an emission s ource PM that contains similar to 10% by weight of soluble transition metal s, was added (0-200 mug/ml) to BALF or sELF and exposed to 20% O-18(2) (24 degreesC, 4 h). Oxygen incorporation was quantified as excess O-18 in the d ried samples after incubation. BALF and diluted sELF yielded similar result s. Oxygen incorporation was increased by ROFA addition and was enhanced by ascorbic acid (AA) and mixtures of AA and glutathione (GSH). AA depletion, but not depletion of GSH or uric acid, occurred in parallel with oxygen inc orporation. AA became inhibitory to oxygen incorporation when it was presen t in high enough concentrations that it was not depleted by ROFA. Physiolog ical and higher concentrations of catalase, superoxide dismutase, and gluta thione peroxidase had no effect on oxygen incorporation. Both protein and l ipid were found to be targets for oxygen incorporation; however, lipid appe ared to be necessary for protein oxygen incorporation to occur. Based on th ese findings, we predict that ROFA would initiate significant oxidation of lung lining fluids after in vivo exposure and that AA, GSH, and lipid conce ntrations of these fluids are important determinants of this oxidation.