Endothelial cell injury induced by plasmin in vitro.
We investigated the effect of plasmin on the integrity and function of endothelial cells to elucidate the mechanism by which bleeding or rethrombosis may be induced in thrombolytic therapy. When incubated with cultured human umbilical vein endothelial cells (HUVECs), plasmin increased the endothelial permeability to serum albumin 10 minutes after the incubation. Plasmin damaged the cell membranes 30 minutes after the incubation, detached the cells from the matrix 3 hours after the incubation, and finally induced cell lysis. Such damaging effects on HUVECs were not observed with plasminogen or plasmin pretreated with aprotinin and alpha 2-plasmin inhibitor, suggesting that the catalytic function of plasmin plays an important role in inducing this damage. Sulfur 35-labeled glycosaminoglycans (35S-GAGs) of HUVECs were decreased 1 hour after the incubation of plasmin with HUVECs, and the thrombomodulin (TM) activity of HUVECs measured by protein C activation capacity was decreased 6 hours after the incubation. Neither 35S-GAGs nor the TM activity of HUVECs was decreased after the incubation of plasmin pretreated with aprotinin and alpha 2-plasmin inhibitor. These findings suggest that the nonthrombogenic properties of endothelial cells can be damaged by the proteolytic action of plasmin. Our findings, taken together, suggest that plasmin damages the endothelial barrier function, endothelial cell integrity, and nonthrombogenic properties. These damaging effects of plasmin on endothelial cells may be related to the pathophysiology of bleeding or rethrombosis observed in patients undergoing high-dose thrombolytic therapy for thrombosis.
Okajima
K
K
Departments of Laboratory Medicine and Medicine, Kumamoto University Medical School, Japan.
Abe
H
H
Binder
B R
BR
D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005341:Fibrinolysin / Q000633:toxicity*; D006025:Glycosaminoglycans / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D012709:Serum Albumin / Q000378:metabolism; D015912:Thrombolytic Therapy / Q000009:adverse effects; D013927:Thrombosis / Q000139:chemically induced; D013997:Time Factors; D014471:Umbilical Veins
D006025:Glycosaminoglycans; D012709:Serum Albumin; D006735:Horseradish Peroxidase; D005341:Fibrinolysin