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Diesel exhaust particulate matter induces multinucleate cells and zinc transporter-dependent apoptosis in human airway cells.

Ackland ML, Zou L, Freestone D, van de Waasenburg S, Michalczyk AA

1Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, Burwood, Victoria, Australia.

The cellular effects of biodiesel emissions particulate matter (BDEP) and petroleum diesel emissions particulate matter (PDEP) were compared using a human airway cell line, A549. At concentrations of 25 mug/ml, diesel particulate matter induced the formation of multinucleate cells. In cells treated with a mixture of 80% PDEP:20% BDEP, 52% of cells were multinucleate cells compared with only 16% of cells treated with 20% PDEP:80% BDEP with a background multinucleate rate of 7%. These results demonstrate a causal relation between the formation of multinucleate cells and exposure to exhaust particulate matter, in particular diesel exhaust. Exposure of A549 cells to PDEP induced apoptosis, seen by active caspase-3 expression and the presence of cleaved pancytokeratin. PDEP exhaust was a much stronger inducer of cellular death through apoptosis than BDEP. There was an eightfold increase in the expression of SLC30A3 (zinc transporter-3 or ZnT3) in cells exposed to 80% PDEP:20% BDEP compared to untreated cells. The increase in ZnT3 expression seen in apoptotic cells following PDEP suggests a role for this zinc transporter in the apoptotic pathway, possibly through controlling zinc fluxes. As exposure to diesel exhaust particles is associated with asthma and apoptosis in airway cells, diesel exhaust particles may directly contribute to asthma by inducing epithelial cell death through apoptotic pathway.Immunology and Cell Biology (2007) 85, 617-622; doi:10.1038/sj.icb.7100109; published online 7 August 2007.

Published 6 December 2007 in Immunol Cell Biol, 85(8): 617-22.
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