The pathophysiology of superoxide: roles in inflammation and ischemia.
The superoxide radical plays major roles in the neutrophil-medicated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite different in these two pathological states. While neutrophils produce superoxide for the primary purpose of aiding in the killing of ingested microbes, a second useful function has evolved. The superoxide released from actively phagocytosing neutrophils serves to attract more neutrophils by reacting with, and activating, a latent chemotactic factor present in plasma. Superoxide dismutase, by preventing the activation of this superoxide-dependent chemotactic factor, exerts potent anti-inflammatory action. During ischemia, energy-starved tissues catabolize ATP to hypoxanthine. Calcium transients in these cells appear to activate a calmodulin regulated protease which attacks the enzyme xanthine dehydrogenase, converting it to a xanthine oxidase capable of superoxide generation. When the tissue is reperfused and reoxygenated, all the necessary components are present (xanthine oxidase, hypoxanthine, and oxygen) to produce a burst of superoxide which results in extensive tissue damage. Ischemic tissues are protected by superoxide dismutase or allupurinol, an inhibitor of xanthine oxidase.
D000818:Animals; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D009393:Nephritis / Q000188:drug therapy; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000627:therapeutic use; D013481:Superoxides / Q000502:physiology*; D014969:Xanthine Oxidase / Q000502:physiology
D005609:Free Radicals; D013481:Superoxides; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen