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Fine ambient particles induce oxidative stress and metal binding genes in human alveolar machrophages
Citation:
HUANG, Y. T., Z. Li, J. D. CARTER, J. M. SOUKUP, D. A. Schwartz, AND I. V. Yang. Fine ambient particles induce oxidative stress and metal binding genes in human alveolar machrophages. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. American Thoracic Society, New York, NY, 41(5):544-552, (2009).
Impact/Purpose:
research results
Description:
Exposure to ambient pollutant particles (APP) increased respiratory morbidity and mortality. The alveolar macrophages (AMs) are one cell type in the lung directly exposed to APP. Upon contact with APP, AMs are activated and produce reactive oxygen species, but the scope ofthis oxidative stress response remains poorly defined. In this study, we determined the gene expression profile in human AMs exposed to APP and sought to characterize the global response ofpro-and anti-oxidant genes. We exposed AMs obtained by bronchoscopy from normal individuals to Chapel Hill PM2.S (1 ug/ml) or vehicle for 4 hours (n = 6 independent samples each). mRNAs were extracted, amplified and hybridized to Agilent Human 1A microarraySignificant genes were identified by 0 Statistical Analysis for Microarrays (SAM) (FDR 10%, P :s 0.05) and mapped to Gene Ontology (GO) based on their molecular functions. We found 34 and 41 up-and down¬regulated genes respectively. Twenty-two genes (-30%) were involved in metal binding and 14 were linked to oxidative stress, including upregulation of 5 metallothionein-l (MTI) isoform genes. Exogenous MTIF protein attenuated PM2.s-induced H202 production while knockdown ofMTIF gene expression increased H202 production induced by PM2.so Our microarray results in human AMs showed a gene expression profile most notable for genes related to metal binding and oxidative stress, especially MTI isoform genes, after in vitro PM2.S exposure. These findings suggest that metals associated with ambient particles, e.g., zinc, copper, and arsenic, induce MTI and may playa primary role in particle-induced oxidative stress. Key words: particulate matter, air pollution, microarray, metallothionein, zinc, copper, arsenic
