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CONCENTRATED AMBIENT AIR POLLUTION CREATES OXIDATIVE STRESS IN CNS MICROGLIA.
Veronesi, B, O. Makwana, M. Pooler, J. Carter, J E. Royland, AND L. C. Chen. CONCENTRATED AMBIENT AIR POLLUTION CREATES OXIDATIVE STRESS IN CNS MICROGLIA. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Nanometer size particles carry free radical activity on their surface and can produce oxidative stress (OS)-mediated damage upon impact to target cells. The initiating event of phage cell activation (i.e., the oxidative burst) is unknown, although many proximal events have been identified (e.g., phagocytosis, increases in NADPH oxidase and NF-kB activity). Data generated in an immortalized microglia cell line (BV2) suggest a role for electrostatic surface charge in this activation. Nanometer size, spherical polystyrene micelle (SPM) beads, coated with either carboxyl (COOH-) or dimethyl amino ((CH3)2-N-) functional groups, measured 860 nm and 850 nm in diameter, respectively. Confluent BV2 cells were labeled with a H2HFF-based fluoroprobe that fluoresces in the presence of the reactive oxygen species, H202. Kinetic readings, collected on cells exposed to either COOH- or (CH3)2-N- coated SPM showed significantly higher fluorescence relative to baseline, in a concentration-response fashion. Subsequent experiments demonstrated that both COOH- and (CH3)2-N- labeled SPM stimulated significant levels of IL-1 and TNF after 6 and 24 hr, respectively. Confocal microscopy was used to document the translocation of FITC-labeled COOH- SPM as they entered the microglia and formed large aggregate populations within the cytoplasm over a 24 hr period. Efforts are underway to determine if charge can stimulate other inflammatory changes proximal to the cytokine release in microglia and macrophages. Previous studies (Veronesi et al., 2003) reported that COOH- and (CH3)2-N- SPM could stimulate cytokines and their message in human epithelial cells, a phenomenon thought to be mediated through ASICS and VR1 receptors. It is currently unknown whether these or other charge sensitive (e.g., scavenger) receptors are involved in the electrostatic activation of phage cells. (This abstract has been reviewed by the USEPA, NHEERL and does not necessarily reflect its policy).
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
CELLULAR AND MOLECULAR TOXICOLOGY BRANCH