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EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN MACROPHAGE RESPONSIVENESS TO LIPOPOLYSACCHARIDE
Citation:
Mundandhara, S. AND M. C. Madden. EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN MACROPHAGE RESPONSIVENESS TO LIPOPOLYSACCHARIDE. Presented at North Carolina Society of Toxiocology Award Competition, Durham, NC, October 16, 2003.
Description:
EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN MACROPHAGE RESPONSIVENESS TO LIPOPOLYSACCHARIDE
S. Mundandhara1 and M.C. Madden2, 1UNC Center for Environmental Medicine, Asthma, and Lung Biology, 2US EPA, NHEERL, Human Studies Division, Chapel Hill, NC, USA
Epidemiological studies have associated exposure to ambient air particulate matter (PM) with increased mortality, including increased hospitalizations for lung infections. Diesel exhaust particles (DEP) account for a significant fraction of the PM in some locations. Alveolar macrophages (AM) function in pulmonary host defense mechanisms against infections via activation and release of soluble mediators. This study was designed to investigate the effects of DEP on human AM functions. AM were exposed in vitro to Standard Reference Material (SRM) 2975 (DEP#1), SRM 1650 (DEP#2), SRM 1975 (a methylene chloride-extract of SRM 2975; DEP#3) (SRMs from National Institute of Standards and Technology), or carbon black (CB) for 24 hr. The concentrations of tumor necrosis factor (TNF ), interleukin 8 (IL8) and prostaglandin E2 (PGE2) were measured in the supernatant by ELISA. Exposures up to 200 g/ml did not affect AM viability except for DEP#2 (containing the greatest organic content) which was cytotoxic at >100 g/ml. 200 g/ml DEP#1 increased the production of TNF and PGE2 which was partially attenuated by pretreating SRM 2975 with the LPS-binding agent polymyxin B. After exposure, AM were incubated with lipopolysaccharide (LPS). In a dose-dependent manner, SRM 2975, SRM 1650 and SRM 1975, but not CB, decreased the ability of LPS to stimulate the production of TNF , IL 8 and PGE2. To examine if the DEPs induced alterations in LPS receptor signaling, after DEP exposure AM were incubated with increasing concentrations of LPS (1-1000 ng/ml), and mediators measured. The data show an attenuation of DEPs-induced decreases in cytokine production with increasing LPS concentrations, suggesting the DEPs, or some component of the DEPs, may interfere with LPS receptor signaling. The data from our study indicate DEPs suppress the ability of AM to produce mediators to LPS. This suppression could impair lung host defense mechanisms. This inhibitory effect appears to be due to organic components rather than the carbonaceous core of DEPs. [This abstract may not represent official EPA policy. Supported, in part, by CR829522]