TY - JOUR
T1 - Myeloperoxidase-catalyzed inactivation of α 1-protease inhibitor by human neutrophils
AU - Clark, R. A.
AU - Stone, P. J.
AU - El Hag, A.
AU - Calore, J. D.
AU - Franzblau, C.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 1981
Y1 - 1981
N2 - We have examined the effect of the myeloperoxidase-hydrogen peroxide-halide system and of activated human neutrophils on the ability of serum α 1-protease inhibitor (α 1-PI) to bind and inhibit porcine pancreatic elastase. Exposure to the isolated myeloperoxidase system resulted in nearly complete inactivation of α 1-PI. Inactivation was rapid (10 to 20 s); required active myeloperoxidase, micromolar concentrations of H 2O 2 (or glucose oxidase as a peroxide generator), and a halide cofactor (Cl - or I -); and was blocked by azide, cyanide, and catalase. Intact neutrophils similarly inactivated α 1-PI over the course of 5 to 10 min. Inactivation required the neutrophils, a halide (Cl -), and a phorbol ester to activate secretory and metabolic activity. It was inhibited by azide, cyanide, and catalase, but not by superoxide dismutase. Neutrophils with absent myeloperoxidase or impaired oxidative metabolism (chronic granulomatous disease) failed to inactivate α 1-PI, and these defects were specifically corrected by the addition of myeloperoxidase or H 2O 2 respectively. Thus, stimulated neutrophils secrete myeloperoxidase and H 2O 2 which combine with a halide to inactivate α 1-PI. We suggest that leukocyte-derived oxidants, especially the myeloperoxidase system, may contribute to proteolytic tissue injury, for example in elastase-induced pulmonary emphysema, by oxidative inactivation of protective antiproteases.
AB - We have examined the effect of the myeloperoxidase-hydrogen peroxide-halide system and of activated human neutrophils on the ability of serum α 1-protease inhibitor (α 1-PI) to bind and inhibit porcine pancreatic elastase. Exposure to the isolated myeloperoxidase system resulted in nearly complete inactivation of α 1-PI. Inactivation was rapid (10 to 20 s); required active myeloperoxidase, micromolar concentrations of H 2O 2 (or glucose oxidase as a peroxide generator), and a halide cofactor (Cl - or I -); and was blocked by azide, cyanide, and catalase. Intact neutrophils similarly inactivated α 1-PI over the course of 5 to 10 min. Inactivation required the neutrophils, a halide (Cl -), and a phorbol ester to activate secretory and metabolic activity. It was inhibited by azide, cyanide, and catalase, but not by superoxide dismutase. Neutrophils with absent myeloperoxidase or impaired oxidative metabolism (chronic granulomatous disease) failed to inactivate α 1-PI, and these defects were specifically corrected by the addition of myeloperoxidase or H 2O 2 respectively. Thus, stimulated neutrophils secrete myeloperoxidase and H 2O 2 which combine with a halide to inactivate α 1-PI. We suggest that leukocyte-derived oxidants, especially the myeloperoxidase system, may contribute to proteolytic tissue injury, for example in elastase-induced pulmonary emphysema, by oxidative inactivation of protective antiproteases.
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M3 - Article
C2 - 6162845
AN - SCOPUS:0019420812
SN - 0021-9258
VL - 256
SP - 3348
EP - 3353
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 7
ER -