Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan.

Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. Research Abstract Details 

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Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. Abstract Text:

Fei Gao,Jeffrey R Koenitzer,Jacob M Tobolewski,Dianhua Jiang,Jiurong Liang,Paul W Noble,Tim D Oury,

Extracellular superoxide dismutase (EC-SOD) is expressed at high levels in lungs. EC-SOD has a polycationic matrix-binding domain that binds to polyanionic constituents in the matrix. Previous studies indicate that EC-SOD protects the lung in both bleomycin- and asbestos-induced models of pulmonary fibrosis. Although the mechanism of EC-SOD protection is not fully understood, these studies indicate that EC-SOD plays an important role in regulating inflammatory responses to pulmonary injury. Hyaluronan is a polyanionic high molecular mass polysaccharide found in the extracellular matrix that is sensitive to oxidant-mediated fragmentation. Recent studies found that elevated levels of low molecular mass hyaluronan are associated with inflammatory conditions. We hypothesize that EC-SOD may inhibit pulmonary inflammation in part by preventing superoxide-mediated fragmentation of hyaluronan to low molecular mass fragments. We found that EC-SOD directly binds to hyaluronan and significantly inhibits oxidant-induced degradation of this glycosaminoglycan. In vitro human polymorphic neutrophil chemotaxis studies indicate that oxidative fragmentation of hyaluronan results in polymorphic neutrophil chemotaxis and that EC-SOD can completely prevent this response. Intratracheal injection of crocidolite asbestos in mice leads to pulmonary inflammation and injury that is enhanced in EC-SOD knock-out mice. Notably, hyaluronan levels are increased in the bronchoalveolar lavage fluid after asbestos-induced pulmonary injury, and this response is markedly enhanced in EC-SOD knock-out mice. These data indicate that inhibition of oxidative hyaluronan fragmentation probably represents one mechanism by which EC-SOD inhibits inflammation in response to lung injury.

Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. Publishing Authors By Initials

F Gao,JR Koenitzer,JM Tobolewski,D Jiang,J Liang,PW Noble,TD Oury,

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Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of biological chemistry

VOLUME: 283

Page Numbers: 6058-66

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 28

MONTH: 12

YEAR: 2007

Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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AFFILIATION: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.

Country: United States

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MEDLINETA: J Biol Chem

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