Published ahead of print on July 15, 2004, doi:10.1165/rcmb.2004-0057OC
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-SODdeficient 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 , keratinocyte-derived chemokines, and macrophage inflammatory protein-2 as well as expression of lung intercellular adhesion molecule1, vascular cell adhesion molecule1, 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 B, NF- 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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