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Urban Particle-induced Apoptosis and Phenotype Shifts in Human Alveolar Macrophages Andrij Holian, Raymond F. Hamilton, Jr., Maria T. Morandi, Steven D. Brown, and Li Li Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Toxicology Program, University of Texas Houston Health Science Center, Houston, TX 77030 USA Abstract
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 cardiovascular disease 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, cell death 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 µg/ml, urban particles had no effect except at 200 µg/ml, and MSH had no effect at 200 µg/ml. ROFA (25 µg/ml) and particles #1648 or #1649 (100 µg/ml) caused apoptosis of AM by all three criteria, but 200 µg/ml MSH had no effect. Finally, 25 µg/ml ROFA and 100 µg/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. Key words : inflammation, macrophage subpopulations, RFD1, RFD7, ROFA. Environ Health Perspect 106:127-132 (1998) . [Online 23 January 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p127-132holian/ abstract.html Address correspondence to A. Holian, 1.276 MSB, Department of Internal Medicine, University of Texas Houston Health Science Center, 6431 Fannin, Houston, TX 77030 USA. This work was supported by National Institutes of Health grants ES-04804, ES-08583, and M01-RR-02558. Received 10 July 1997 ; accepted 3 November 1997.
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