Annexin II tetramer inhibits plasmin-dependent fibrinolysis.
In this paper, we have characterized the regulation of plasmin activity by annexin II tetramer (AIIt). Plasmin activity was measured by a fibrin lysis assay in which a fibrin polymer was produced from purified components and the extent of polymer lysis was determined by following changes in turbidity. Extrinsic lysis of the fibrin polymer, initiated by addition of tissue plasminogen activator (t-PA), was totally blocked if AIIt was present during fibrin polymer formation. Furthermore, fibrin polymer formed in the presence of AIIt was resistant to extrinsic lysis initiated by addition of plasmin. AIIt bound to fibrin polymer under conditions in which polymer lysis was inhibited. Plasmin-dependent extrinsic lysis of the fibrin polymer was also blocked if AIIt was present in the incubation medium, and under these conditions the amidolytic activity of plasmin, measured with an artificial substrate, was inhibited about 5-fold. In contrast, in the absence of fibrin, and at an AIIt/plasmin molar ratio of 526, the amidolytic activity of plasmin was inhibited by only 22.3% +/- 7.4% (mean +/- SD, n = 5) by AIIt. Plasmin-dependent fibrinolysis was only slightly inhibited if fibrin polymer was formed in the presence of annexins I, II, V, or VI. These results identify AIIt as an in vitro regulator of plasmin activity.
Choi
K S
KS
Cancer Biology Research Group, Department of Medical Biochemistry, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Ghuman
J
J
Kassam
G
G
Kang
H M
HM
Fitzpatrick
S L
SL
Waisman
D M
DM
D000577:Amides / Q000378:metabolism; D017306:Annexin A2 / Q000737:chemistry / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000494:pharmacology*; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects*; D006868:Hydrolysis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D000577:Amides; D017306:Annexin A2; D000933:Antifibrinolytic Agents; D002135:Calcium-Binding Proteins; D015842:Serine Proteinase Inhibitors; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin