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Inflammatory cells as a source of airspace extracellular superoxide dismutase after pulmonary injury.

Tan RJ, Lee JS, Manni ML, Fattman CL, Tobolewski JM, Zheng M, Kolls JK, Martin TR, Oury TD

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Extracellular superoxide dismutase (EC-SOD) is an antioxidant abundant in the lung. Previous studies demonstrated depletion of lung parenchymal EC-SOD in mouse models of interstitial lung disease coinciding with an accumulation of EC-SOD in airspaces. EC-SOD sticks to the matrix by a proteolytically sensitive heparin-binding domain; therefore, we hypothesized that interstitial inflammation and matrix remodeling contribute to proteolytic redistribution of EC-SOD from lung parenchyma into the airspaces. To determine if inflammation limited to airspaces leads to EC-SOD redistribution, we examined a bacterial pneumonia model. This model led to increases in airspace polymorphonuclear leukocytes staining strongly for EC-SOD. EC-SOD accumulated in airspaces at 24 h without depletion of EC-SOD from lung parenchyma. This led us to hypothesize that airspace EC-SOD was released from inflammatory cells and was not a redistribution of matrix EC-SOD. To test this hypothesis, transgenic mice with lung-specific expression of human EC-SOD were treated with asbestos or bleomycin to initiate an interstitial lung injury. In these studies, EC-SOD accumulating in airspaces was entirely the mouse isoform, demonstrating an extrapulmonary source (inflammatory cells) for this EC-SOD. We also demonstrate that EC-SOD knockout mice possess greater lung inflammation in response to bleomycin and bacteria when compared with wild types. We conclude that the source of accumulating EC-SOD in airspaces in interstitial lung disease is inflammatory cells and not the lung and that interstitial processes such as those found in pulmonary fibrosis are required to remove EC-SOD from lung matrix.

Published 19 January 2006 in Am J Respir Cell Mol Biol, 34(2): 226-32.
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