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Urate causes the human polymorphonuclear leukocyte to secrete superoxide.
1Department of Biochemistry, Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, NC 27103.
Free Radical Biology & Medicine
|January 1, 1992
Summary
Uric acid triggers human white blood cells to produce oxidants like superoxide (O2-.) and hydrogen peroxide (H2O2). These reactive oxygen species contribute to inflammation, potentially explaining the inflammatory processes in gout.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Polymorphonuclear leukocytes are key immune cells involved in inflammation.
- Uric acid is a metabolic byproduct implicated in inflammatory conditions like gout.
- Reactive oxygen species (ROS) play a dual role in cellular processes and inflammation.
Purpose of the Study:
- To investigate the role of uric acid in stimulating oxidant generation by human polymorphonuclear leukocytes.
- To elucidate the specific oxidants produced and their potential contribution to inflammation.
Main Methods:
- Incubation of human polymorphonuclear leukocytes with uric acid.
- Measurement of superoxide (O2-.) and hydrogen peroxide (H2O2) production.
- Analysis of potential downstream reactive oxygen species formation.
Main Results:
- Uric acid treatment induced significant generation of superoxide (O2-.) and hydrogen peroxide (H2O2) by leukocytes.
- The study suggests a transition metal-catalyzed reaction producing hydroxyl radicals.
- Myeloperoxidase activity was shown to convert H2O2 and chloride into hypochlorous acid.
Conclusions:
- Uric acid stimulates human leukocytes to produce a cascade of reactive oxygen species.
- These uric acid-induced oxidants, including hypochlorous acid, are likely major contributors to the inflammatory response observed in gout.