title: Involvement of protease inhibitors in staphylokinase-induced fibrin-specific fibrinolysis.
abstract: We compared the fibrinolytic properties of recombinant staphylokinase (SAK), a fibrin-specific plasminogen activator, with those of streptokinase and tissue-type plasminogen activator (t-PA) by means of the amidolytic method. We also investigated the involvement of alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin in SAK-induced fibrin-specific fibrinolysis. Both SAK and t-PA activated plasminogen efficiently in the presence of fibrin in human plasma. Although t-PA activated plasminogen dependently on fibrin in the reconstituted plasma system, SAK activated plasminogen independently of fibrin without alpha 2-plasmin inhibitor (alpha 2-antiplasmin, alpha 2-PI). These findings suggest that fibrin and alpha 2-PI play important roles in plasminogen activation by SAK but not by t-PA. Furthermore, protease inhibitors such as alpha 2-PI, alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin inhibited plasminogen activation by SAK and the inhibitory actions of these protease inhibitors disappeared in the presence of fibrin. This shows that alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin, other than alpha 2-PI, contribute to the fibrin-specificity of SAK.
authors.affiliation: Yakult Central Institute for Microbiological Research, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shishido
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.forename: N
authors.initials: N
authors.lastname: Kaneda
authors.forename: H
authors.initials: H
authors.lastname: Sansawa
authors.forename: K
authors.initials: K
authors.lastname: Shimura
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Yokokura
mesh_terms: D000595:Amino Acid Sequence; D002852:Chromatography, Ion Exchange; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D011994:Recombinant Proteins; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus