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COMPARATIVE TOXICITY OF DIFFERENT EMISSION PARTICLES IN MURINE PULMONARY EPITHELIAL CELLS AND MACROPHAGES
Citation:
Stevens, T., M. J. Daniels, P. Singh, AND M I. Gilmour. COMPARATIVE TOXICITY OF DIFFERENT EMISSION PARTICLES IN MURINE PULMONARY EPITHELIAL CELLS AND MACROPHAGES. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Comparative Toxicity of Different Emission Particles in Murine Pulmonary Epithelial Cells and Macrophages. T Stevens1, M Daniels2, P Singh2, M I Gilmour2. 1 UNC, Chapel Hill 27599 2Experimental Toxicology Division, NHEERL, RTP, NC 27711
Epidemiological studies have shown a correlation between levels of particular matter (PM) and hospital admissions and mortality due to respiratory illness. The chemical components of PM responsible for these effects are not known. This study investigated the ability of diesel exhaust particles (DEP) and fine coal fly ash (CFA) from different sources to cause injury and activation of lung cells. Murine pulmonary macrophages and epithelial cell lines were exposed for 1, 4, or 24 hours with varying doses of NIST 2975, Japanese DEP, German DEP, W Kentucky fine CFA, or Montana fine CFA (10 ug/ml, 50 ug/ml, or 150 ug/ml) as well as vehicle control and endotoxin (0.2 ug/ml, 1 ug/ml, or 5 ug/ml). After exposure, biochemical markers of cytotoxicity, lactate dehydrogenase (LDH) and ATP production, and pro-inflammatory cytokines (TNF-a, MIP-2, IL-6, and IL-1) were analyzed. Overall, the DEPs caused more cytotoxicity than the CFA samples, and macrophages were more sensitive than epithelial cells. ATP effects were stronger and seen at earlier time points demonstrating this assay to be more sensitive than LDH. No differences in cytokine levels were observed in the epithelial cells of any treatment group. Each cytokine was greatly increased in LPS-exposed macrophages but showed variable patterns with the PM exposure treatments across time and concentration. While some increases were noted there was a general decrease in cytokine output as exposure concentrations increased which may be related to either the decrease in ATP levels, or increased binding or quenching of cytokine by the particulates. We conclude that measurement of ATP levels in the murine macrophage cell line was the most sensitive endpoint of PM effects and that DEP fractions are more potent than CFA samples. Measurement of cell products such as cytokines may be confounded by changes in metabolic activity or physical interaction with the materials under study. (Supported by NIEHS T32ESO7126-21A, This abstract does not reflect EPA policy.)