A mechanism for inhibition of luminol-dependent neutrophil chemiluminescence by polyanions.
Heparin has been reported to have antiinflammatory properties in both experimental animal and human disease states. Previous investigators assumed that the antiinflammatory properties of heparin were related to its anticoagulant effect. In this study we confirm the ability of heparin to inhibit luminol-dependent chemiluminescence by neutrophils stimulated with serum-activated zymosan. This inhibition is due to a combination of the diminished release of myeloperoxidase and the scavenging of the luminol oxidant generated by the myeloperoxidase-H2O2-chloride system. Although the polyanions heparin and dextran sulfate were effective in inhibiting luminol-dependent myeloperoxidase-H2O2-chloride chemiluminescence, the uncharged polysaccharide dextran T500 was without effect. None of the polysaccharides inhibited oxygen consumption by stimulated neutrophils. Additionally, heparin was able to reduce the myeloperoxidase release from zymosan-stimulated neutrophils by nearly 50%. Recent studies have shown that some antiinflammatory drugs scavenge peroxidase-generated oxidants of luminol. Such a property may explain the previously observed antiinflammatory effects of heparin and other polyanions.
D003574:Cytochrome c Group / Q000097:blood; D003864:Depression, Chemical; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology*; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D009195:Peroxidase / Q000097:blood; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000097:blood
D003574:Cytochrome c Group; D016264:Dextran Sulfate; D003911:Dextrans; D006493:Heparin; D007770:L-Lactate Dehydrogenase; D008165:Luminol; D009195:Peroxidase; D000071228:Polyelectrolytes; D011108:Polymers; D011724:Pyridazines; D014969:Xanthine Oxidase