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Published ahead of print on July 15, 2004, doi:10.1165/rcmb.2004-0057OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 31, pp. 432-439, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2004-0057OC

Extracellular Superoxide Dismutase Attenuates Lipopolysaccharide-Induced Neutrophilic Inflammation

Russell P. Bowler, Mike Nicks, Karen Tran, Grant Tanner, Ling-Yi Chang, Scott K. Young and G. Scott Worthen

Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado

Address correspondence to: Russell P. Bowler, M.D., Ph.D., National Jewish Medical and Research Center, K736a, 1400 Jackson Street, Denver, CO 80206. E-mail: BowlerR{at}njc.org

Extracellular superoxide dismutase (EC-SOD) is an abundant antioxidant in the lung and vascular walls. Previous studies have shown that EC-SOD attenuates lung injury in a diverse variety of lung injury models. In this study, we examined the role of EC-SOD in mediating lipopolysaccharide (LPS)-induced lung inflammation. We found that LPS-induced neutrophilic lung inflammation was exaggerated in EC-SOD–deficient mice and diminished in mice that overexpressed EC-SOD specifically in the lung. Similar patterns were seen for bronchoalveolar lavage cytokines, such as tumor necrosis factor–{alpha}, keratinocyte-derived chemokines, and macrophage inflammatory protein-2 as well as expression of lung intercellular adhesion molecule–1, vascular cell adhesion molecule–1, endothelial cell selectin, and platelet selectin. In a macrophage cell line, EC-SOD inhibited LPS-induced macrophage cytokine release, but did not alter expression of intercellular adhesion molecules in endothelial cells. These results suggest that EC-SOD plays an important role in attenuating the inflammatory response in the lung most likely by decreasing release of proinflammatory cytokines from phagocytes.

Abbreviations: bronchoalveolar lavage, BAL • BAL fluid, BALF • extracellular superoxide dismutase, EC-SOD • endothelial cell selectin, E-selectin • fluorescence-activated cell sorter buffer, FB • intercellular adhesion molecule, ICAM • interleukin, IL • keratinocyte-derived chemokines, KC • lipopolysaccharide, LPS • macrophage inflammatory protein, MIP • myeloperoxidase, MPO • nuclear factor–{kappa}B, NF-{kappa}B • phosphate-buffered saline, PBS • platelet selectin, P-selectin • reactive oxygen species, ROS • superoxide dismutase, SOD • tumor necrosis factor, TNF • vascular cell adhesion molecule, VCAM




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