EFFECT OF ANTIINFLAMMATORY DRUGS ON MYELOPEROXIDASE-DEPENDENT HYDROXYL RADICAL GENERATION BY HUMAN NEUTROPHILS

Neutrophils comprise a group of leukocytes that play a pivotal role in inflammation and vascular diseases like ischemia/reperfusion. These a ctivated phagocytic cells are drawn to the site of injury, secreting s uperoxide and other oxidants derived from the formation of this free r adical. This series of events frequently results in localized tissue d amage. Surprisingly, free radical scavengers frequently offer only min imal relief. Why this is so may be due, in part, to our limited unders tanding of mechanisms that govern generation of free radicals in these settings. Although the metal ion-catalyzed Haber-Weiss reaction is co nsidered the classical pathway for neutrophil-derived hydroxyl radical , an alternative mechanism, such as the myeloperoxidase-dependent path way, may undoubtedly contribute to the formation of this free radical by stimulated neutrophils. In this study, we explored this possibility by investigating the role of different classes of anti-inflammatory d rugs to ameliorate; hydroxyl radical generation via the myeloperoxidas e-dependent pathway. In this paper, we report that meclofenamic acid i nhibited myeloperoxidase-dependent hydroxyl radical generation through scavenging of hypochlorous acid and not by direct inhibition of myelo peroxidase. The importance of these results with regard to the clinica l efficacy of this anti-inflammatory compound remains to be determined as studies into the significance of myeloperoxidase-dependent hydroxy l radical formation in inflammatory tissue injury continue.