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Published ahead of print on January 26, 2006, doi:10.1165/rcmb.2005-0329OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 6, June 2006, 670-676

A more recent version of this article appeared on June 1, 2006
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Submitted on August 29, 2005
Revised on January 20, 2006

Airborne Particulate Matter Inhibits Alveolar Fluid Reabsorption in Mice via Oxidant Generation

Gokhan M Mutlu1, Colleen Snyder1, Amy Bellmeyer1, Helena Wang1, Keenan Hawkins1, Saul Soberanes1, Lynn C Welch1, Andrew J Ghio2, Navdeep S Chandel1, David W Kamp1, Jacob I Sznajder1, and G.R. Scott Budinger1*

1 Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL, USA, 2 National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA

* To whom correspondence should be addressed. E-mail: sbuding{at}northwestern.edu.

Rationale. Ambient particulate matter is increasingly recognized as a significant contributor to human cardiopulmonary morbidity and mortality in the United States and worldwide. Objectives. We sought to determine whether exposure to ambient particulate matter would alter alveolar fluid clearance in mice. Methods. Mice were exposed to a range of doses of a well-characterized particulate matter collected from the ambient air in Dusseldorf, Germany through a single intratracheal instillation and alveolar fluid clearance and measurements of lung injury were made. Measurements and Main Results. Exposure to even very low doses of particulate matter (10 µg) resulted in a significant reduction in alveolar fluid clearance that was maximal 24 hours after the exposure with complete resolution after 7 days. This was paralleled by a decrease in lung Na,K-ATPase activity. To investigate the mechanism of this effect, we measured plasma membrane Na, K-ATPase abundance in A549 cells and Na, K-ATPase activity in primary rat alveolar type II cells following exposure to particulate matter in the presence or abscence of the combined superoxide dismutase and catalase mimetic EUK-134 (5µM). Membrane but not total protein abundance of the Na, K-ATPase was decreased following exposure to particulate matter as was Na, KATPase activity. This decrease was prevented by the combined superoxide dismutase/catalase mimetic EUK-134. Conclusion. The intratracheal instillation of particulate matter results in alveolar epithelial injury and decreased alveolar fluid clearance conceivably due to downregulation of the Na, K-ATPase.




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