HUMAN METHIONINE SULFOXIDE-PEPTIDE REDUCTASE, AN ENZYME CAPABLE OF REACTIVATING OXIDIZED ALPHA-1-PROTEINASE INHIBITOR INVITRO

Abstract

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 was demonstrated. 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 (.alpha.1Pl) oxidized by treatment with chloramine T or a myeloperoxidase oxidizing system. The PMN-derived enzyme does not reactivate .alpha.1Pl inactivated by treatment in vitro with aqueous solutions of cigarette smoke plus peroxide. After the instillation of oxidized human .alpha.1Pl into lungs of normal or ozone-tolerant rats, no reactivated .alpha.1Pl was found in the pulmonary lavage obtained from these animals. Patients with chronic obstructive pulmonary disease appear to have normal levels of PMN Met(O)peptide reductase.