Proteolytic inactivation of alpha-1-proteinase inhibitor by a neutrophil metalloproteinase. 1988

P E Desrochers, and S J Weiss
Simpson Memorial Research Institute, Department of Internal Medicine, Ann Arbor, Michigan 48109.

Human neutrophils triggered with phorbol myristate acetate or opsonized zymosan particles released a metalloproteinase (MP) capable of cleaving and inactivating alpha-1-proteinase inhibitor (alpha-1-PI). Sequence analysis of the amino acids in proteolyzed, native alpha-1-PI revealed a unique single cleavage site between Phe-352 and Leu-353. An analysis of the process regulating the enzyme's activity revealed that the neutrophil MP was released from cells in a latent form whose activation was tightly linked to the generation of hypochlorous acid. These results indicate that human neutrophils use chlorinated oxidants to activate a latent MP that is capable of proteolytically inactivating alpha-1-PI by cleaving the antiproteinase at a unique point in its inhibitory site region.

UI MeSH Term Description Entries
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D009895 Opsonin Proteins Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate. Opsonin,Opsonin Protein,Opsonins,Protein, Opsonin
D010196 Pancreatic Elastase A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 3.4.21.36. Elastase,Pancreatopeptidase,Elastase I,Pancreatic Elastase I,Elastase I, Pancreatic,Elastase, Pancreatic
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000515 alpha 1-Antitrypsin Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES. Trypsin Inhibitor, alpha 1-Antitrypsin,alpha 1-Protease Inhibitor,alpha 1-Proteinase Inhibitor,A1PI,Prolastin,Serpin A1,Zemaira,alpha 1 Antiprotease,alpha 1-Antiproteinase,1-Antiproteinase, alpha,Antiprotease, alpha 1,Inhibitor, alpha 1-Protease,Inhibitor, alpha 1-Proteinase,Trypsin Inhibitor, alpha 1 Antitrypsin,alpha 1 Antiproteinase,alpha 1 Antitrypsin,alpha 1 Protease Inhibitor,alpha 1 Proteinase Inhibitor

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