Involvement of protease inhibitors in staphylokinase-induced fibrin-specific fibrinolysis.
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.
Shishido
Y
Y
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Sakai
M
M
Kaneda
N
N
Sansawa
H
H
Shimura
K
K
Hashimoto
S
S
Yokokura
T
T
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
D011480:Protease Inhibitors; D011994:Recombinant Proteins; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus