The injurious effect of eosinophil peroxidase, hydrogen peroxide, and halides on pneumocytes in vitro.
Recent data suggest that eosinophils may cause lung injury. To determine if the eosinophil peroxidase (EPO)-hydrogen peroxide (H2O2)-halide system could mediate this injury, we added human EPO, H2O2 (or glucose and glucose oxidase as a continuous source of H2O2), and various halides to monolayers of 51Cr-labeled human A549 and rat type II pneumocytes. Cell lysis was measured as soluble 51Cr release. In initial experiments, EPO in solution did not induce lysis under these conditions. Therefore, in subsequent experiments, pneumocytes were preincubated with EPO for 15 minutes, washed to remove unbound enzyme, and then glucose, glucose oxidase, and the halides were added. EPO alone was not injurious, nor was the addition of glucose and glucose oxidase in the absence of EPO. In contrast, the combined addition of EPO, glucose, glucose oxidase, and chloride produced marked target-cell lysis. This effect was time and EPO dose dependent and was enhanced by the addition of iodide. Catalase and azide substantially inhibited the lysis produced by the EPO-H2O2-halide system, suggesting that EPO-catalyzed products of halide oxidation mediated this form of injury. Finally, the addition of eosinophil major basic protein at 10(-5) mol/L to EPO-coated pneumocytes incubated with glucose, glucose oxidase, and halides failed to enhance or inhibit lysis. We hypothesize that the EPO-H2O2-halide system may injure the lung in asthma and eosinophilic pulmonary syndromes.
D000818:Animals; D001965:Bromides / Q000633:toxicity*; D002374:Catalase / Q000494:pharmacology; D002712:Chlorides / Q000633:toxicity*; D004804:Eosinophils / Q000201:enzymology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007454:Iodides / Q000633:toxicity*; D007700:Kinetics; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000097:blood* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D001965:Bromides; D002712:Chlorides; D007454:Iodides; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase