Epidemiological studies report a small but positive association between short-term increases in airborne particulate matter and small increases in morbidity and mortality from respiratory and cardiovasculardisease in urban areas. However, the lack of a mechanistic explanation to link particle exposure and human health effects makes it difficult to validate the human health effects. The present study tested the hypothesis that urban particles could cause apoptosis of human alveolar macrophages (AM) and a shift of their phenotypes to a higher immune active state, which would provide a mechanism to explain an inflammatory response. Freshly isolated human AM were incubated for 24 hr with urban particles (#1648 and #1649), Mount Saint Helen's ash (MSH), and residual oil fly ash (ROFA). Cell viability was assessed by trypan blue exclusion and apoptosis was demonstrated by morphology, celldeath ELISA, and DNA ladder formation. Additionally, AM were characterized according to RFD1 + (immune stimulatory macrophages) and RFD1 + 7 + (suppressor macrophages) phenotypes by flow cytometry. ROFA particles caused AM necrosis at concentrations as low as 10 5g/ml, urban particles had no effect except at 200 5g/ml, and MSH had no effect at 200 5g/ml. ROFA (25 5g/ml) and particles #1648 or #1649 (100 5g/ml) caused apoptosis of AM by all threecriteria, but 200 5g/ml MSH had no effect. Finally, 25 5g/ml ROFA and 100 5g/ml particles #1648 or #1649 up regulated the expression of the RFD1 + AM phenotype, while only ROFA decreased the RFD1+ 7 + phenotype. Consequently, ROFA and urban particles can induce apoptosis of human AM and increase the ratio of AM phenotypes toward a higher immune active state (i.e., increased RFD1+:RFD1 + 7 + ratio). If urban particles cause similar changes in vivo , this could result in lung inflammation and possible increased pulmonary and cardiovascular disease. [ABSTRACT FROM AUTHOR]