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Mechanisms of inflammatory lung injury
Emphasis is on evaluating the role of free radicals in pulmonary oxidant injury and on evaluating changes in pulmonary structure/function caused by exposure to oxidants or proinflammatory mediators. I am investigating the hypothesis that extracellular superoxide dismutase plays a critical role in controlling inflammation in the lung. EC-SOD scavenges superoxide and is the primary antioxidant enzyme in lung extracellular spaces. In the absence of EC-SOD, superoxide can react with nitric oxide to form peroxynitrite which is a highly reactive pro-inflammatory radical. In the presence of EC-SOD nitric oxide is preserved and acts as the key immunomodulatory agent in the lung. This hypothesis is being tested in both cells and animals using genetically modified cells and transgenic or knock-out animals over- or underexpressing extracellular superoxide dismutase. Novel antioxidant mimetics are being developed and tested as new and potentially effective therapeutic agents. Selected Publications
Kinnula VL, Crapo JD. Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med. 2003 Jun 15;167(12):1600-19. Bowler RP, Arcaroli J, Abraham E, Patel M, Chang LY, Crapo JD. Evidence for extracellular superoxide dismutase as a mediator of hemorrhage-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2003 Apr;284(4):L680-7. Epub 2003 Jan 10. Chang LY, Subramaniam M, Yoder BA, Day BJ, Ellison MC, Sunday ME, Crapo JD. A catalytic antioxidant attenuates alveolar structural remodeling in bronchopulmonary dysplasia. Am Rev Respir Crit Care Med 167:57-64, 2003. Kinnula VL and JD Crapo. Superoxide dismutases in malignant cells and human tumors. (Review) Free Radic Biol Med 36:718-744, 2004. Bowler RP, PJ Barnes and JD Crapo. The role of oxidative stress in chronic obstructive pulmonary disease. J COPD 1:255-277, 2004. |
Faculty
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