Abnormal platelet hydrogen peroxide metabolism in aspirin hypersensitivity.
The generation and degradation of hydrogen peroxide (H2O2) by platelets was investigated in aspirin hypersensitive and tolerant allergic subjects, and compared to that in general medical patients and healthy controls. H2O2 generation following triggering with anti-IgE, specific allergen, and with aspirin (ASA) and indomethacin was examined using a chemiluminescence assay. Platelet levels of the main intracellular enzyme responsible for H2O2 metabolism--glutathione peroxidase--were measured by a quantitative functional assay. H2O2 secretion could be triggered by anti-IgE in platelets from 15/29 ASA-tolerant atopics, and by relevant allergen in platelets passively sensitized with allergen-specific IgE. A similar response was observed following triggering with ASA, and with indomethacin, in platelets from 8/25 ASA-sensitive subjects. Mean platelet glutathione peroxidase activity was significantly lower in subjects with ASA-induced asthma, but not in subjects with non-asthmatic reactions to ASA, compared to all other groups. Within the ASA-sensitive group there was no correlation between low peroxidase activity and ASA-triggered chemiluminescence. Our findings emphasize the heterogeneity of ASA-intolerance syndromes and point to abnormal oxygen/peroxide metabolism as a common pathway underlying ASA-induced asthma.
Pearson
D J
DJ
Department of Medicine, University of Manchester, U.K.
Suarez-Mendez
V J
VJ
D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000097:blood* / Q000139:chemically induced / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D004342:Drug Hypersensitivity / Q000097:blood* / Q000209:etiology / Q000276:immunology; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D007073:Immunoglobulin E / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008163:Luminescent Measurements; D015539:Platelet Activation / Q000187:drug effects
D007073:Immunoglobulin E; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D001241:Aspirin; D007213:Indomethacin