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ELECTROSTATIC CHARGE STIMULATES OXIDATIVE STRESS IN CNS MICROGLIA.
Veronesi, B, M. Pooler, O. Makwana, J. Carter, I. BeckSpeier, AND W. Kreyling. ELECTROSTATIC CHARGE STIMULATES OXIDATIVE STRESS IN CNS MICROGLIA. Presented at Society of Free Radical Biology and Medicine, St. Thomas, U.S. VIRGIN ISLANDS, November 17 - 22, 2004.
Nanometer size particles carry free radical activity on their surface and can create oxidative stress (OS)-mediated inflammatory changes upon impact. The oxidative burst signals the activation of phage-lineage cells such as peripheral macrophages, Kupffer cells and CNS microglia. Although many of the sub-cellular events proximal to the burst have been identified (e.g., phagocytosis, increases in NADPH oxidase and NF-kB activity), its initiating event is unknown. Data, generated in an immortalized microglia cell line (BV2), are presented that support a role for electrostatic charge as the initiating factor. Nanometer sized, 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 (10 minutes), 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-1b 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 LAB
CELLULAR AND MOLECULAR TOXICOLOGY BRANCH