Role of phosphate, pyrophosphate, adenine nucleotides and sulfate in activating production of the superoxide radical by macrophages, and in formation of rat paw edema.

The presence of anions of phosphate (Pi), pyrophosphate (PPi), adenine nucleotides and sulfate greatly enhanced the production of superoxide radical (-O-2) by isolated guinea-pig macrophages. These anions, however, failed to enhance the production of -O-2 by the xanthine oxidase system, suggesting that they serve only as activators of -O-2 generating enzyme(s) located on the macrophage cell membrane. Many other common anions were ineffective in the macrophage system. In the presence of concentrations of Pi, PPi, adenine-5'-triphosphate (ATP) reported to be in the synovial fluid, -O-2 was produced efficiently and was inhibited by diclofenac sodium. These anions induced rat paw edema, maintained the swelling at least up to 6 h. The edema was suppressed partially by repeated injection of superoxide dismutase (SOD). High doses of sodium chloride and nitrate failed to maintain the swelling.