Myeloperoxidase-induced inactivation of α₁-antiprotease in hamsters

While numerous studies have demonstrated that the myeloperoxidase system found in neutrophils can oxidize and functionally inactivate α₁-proteinase inhibitor in vitro, there is little direct evidence that this phenomenon is relevant in vivo. Using incubation with tritiated porcine pancreatic elastase followed by column chromatography to quantitate binding, we demonstrated recovery of microgram amounts of functional α₁-protease inhibitor from broncholveolar lavage of hamster lungs. When exposed to the myeloperoxidase system in vitro, hamster α₁-protease inhibitor was 97% inactivated. Functional α₁-protease inhibitor recovered by bronchoalveolar lavage 20 minutes after hamsters were given intratracheal injections with myeloperoxidase and either hydrogen peroxide or glucose plus glucose oxidase was only half that recovered from control animals. These studies suggest that the myeloperoxidase system is effective in oxidizing α₁-protease inhibitor in vivo. They support the concept that oxidation of α₁-protease inhibitor by myeloperoxidase from neutrophil granules in the presence of H₂O₂ and halide may produce elastase-antielastase imbalance in vivo and contribute to the development of acute lung injury and emphysema in humans.