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Functionally Charged Polystyrene Particles Activate Immortalized Mouse Microglia (BV2): Cellular and Genomic Response
Citation:
VERONESI, B., J. Tajuba, N. Saleh, W. O. WARD, S. D. HESTER, J. D. CARTER, AND G. V. LOWRY. Functionally Charged Polystyrene Particles Activate Immortalized Mouse Microglia (BV2): Cellular and Genomic Response. Journal of Nanotoxicology. Taylor and Francis, Philadelphia, PA, 2(3):130-143, (2008).
Impact/Purpose:
This manuscript examines the relationship between a physical property of nanoparticles (i.e., surface charge) and the biological activation of oxidative stress damage in immortalized microglia, an in vitro model. Data that link the physical properties of nanoparticles (NP) with their biological effects are critical for their safe use and design and for identifying their mode of action (MOA). Such data bases are especially needed by ORD which is currently evaluating the applicability of OPPTS's and OECD’s risk assessment guidelines to regulate NP. Such data will help the Agency better evaluate its current risk assessment framework by identifying NP properties in their regulatory guidelines that influence NP toxicity. The potential OS mediated toxicity of NP with high environmental and consumer exposure will benefit several EPA offices (e.g., OSWER, OW, OPP, and OPPTS). Such research offers a valuable data base to support risk assessment and contribute to understanding the MOA underlying nanotoxicity.
Description:
The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Same size (~850-950 nm) spherical polystyrene microparticles (SPM) with net negative (carboxyl, COOH-) or positive (dimethyl amino, CH3)2-N- zeta potentials were exposed to BV2 microglia (5-20 µl/ml). Both stimulated an oxidative burst, increased Caspase 3/7 activity and caused inflammatory cytokine release. Ultrastructure indicated that SPM particles were phagocytosed as single particles but formed large intra-cellular 4-6 µm agglomerates. Microarray analysis indicated that negatively charged SPM-COOH- affected approximately 146 genes while the positively charged SPM -(CH3)2-N- affected approximately 2580 genes. Only 30 genes were significantly affected in common. Of the 48 genes associated with oxidative stress pathways, 33 genes were coordinately down-regulated by SPM- (CH3)2-N- and up-regulated by SPM-COOH- exposure. Together, these data indicate that functionally charged, inert submicron-size particles differentially activate BV2 microglia along oxidative stress and inflammatory pathways.