Platelet prevention of oxidant lung oedema is not mediated through scavenging of hydrogen peroxide.
Previous studies have shown that washed human platelets attenuate oxidant oedema in isolated perfused rabbit lungs through mechanisms dependent on platelet glutathione. We hypothesized that the platelet glutathione redox cycle scavenges hydrogen peroxide in this model and thereby protects vascular endothelial cells from oxidant injury. This hypothesis was tested by asking two questions: (1) do glutathione-supplemented platelets demonstrate augmented lung protection compared with control platelets, and (2) does conjugation of platelet glutathione with 1-chloro-2,4-dinitrobenzene or inactivation of catalase with 3-amino-1,2,4-triazole decrease in vitro platelet metabolism of hydrogen peroxide? We incubated washed human platelets with reduced glutathione or glutathione monoester and observed platelet glutathione contents of 181% and 189%, respectively, compared with control values. Incubation of platelets with N-acetylcysteine did not alter platelet glutathione content. Infusion of glutathione-supplemented platelets into isolated lungs injured by purine and xanthine oxidase did not augment platelet protection compared with untreated platelets. We also found that conjugation of platelet glutathione and/or inactivation of platelet catalase did not decrease the rate constant for platelet metabolism of hydrogen peroxide. We conclude that platelets attenuate oxidant lung oedema through glutathione-dependent mechanisms other than direct scavenging of hydrogen peroxide.
Godwin
J E
JE
Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston.
Heffner
J E
JE
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011654:Pulmonary Edema / Q000517:prevention & control*; D011687:Purines / Q000494:pharmacology; D011817:Rabbits; D014969:Xanthine Oxidase / Q000494:pharmacology
D004137:Dinitrochlorobenzene; D011687:Purines; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D005978:Glutathione; D000640:Amitrole