Proteolytic inactivation of alpha-1-proteinase inhibitor by a neutrophil metalloproteinase.
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.
Desrochers
P E
PE
Simpson Memorial Research Institute, Department of Internal Medicine, Ann Arbor, Michigan 48109.
Weiss
S J
SJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001798:Blood Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D009895:Opsonin Proteins; D010196:Pancreatic Elastase / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology; D000515:alpha 1-Antitrypsin
D000596:Amino Acids; D001798:Blood Proteins; D009895:Opsonin Proteins; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D015054:Zymosan; D010196:Pancreatic Elastase; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate