Human Methionine Sulfoxide-Peptide Reductase, an Enzyme Capable of Reactivating Oxidized Alpha-1-Proteinase Inhibitor In Vitro1–3

The present study demonstrates the presence of methionine sulfoxide [Met(O)] peptide reductase activity in human lung homogenates and in lysates of polymorphonuclear leukocytes (PMN) and alveolar type II cells. Enzyme activity was not detected in human bronchoalveolar lavage fluid or in pulmonary alveolar macrophage lysates. The Met(O)-peptide reductase derived from PMN is capable of reactivating alpha-1-proteinase inhibitor (α1PI) oxidized by treatment with chloramine-T or a myeloperoxidase oxidizing system. However, the PMN-derived enzyme does not reactivate α1PI inactivated by treatment in vitro with aqueous solutions of cigarette smoke plus peroxide. In addition, after the instillation of oxidized human α1PI into lungs of normal or ozone-tolerant rats, no reactivated α1PI could be found in the pulmonary lavage obtained from these animals. Finally, patients with chronic obstructive pulmonary disease appear to have normal levels of PMN Met(O)-peptide reductase.