Prevention of renal fibrin deposition in endotoxin-induced DIC through inhibition of PAI-1.
Plasminogen activator inhibitor-1 (PAI-1) increases in endotoxemia thus possibly cooperating in altering the hemostatic balance in a prothrombotic direction. The effect of the inhibition of PAI-1 with the monoclonal antibody MA-33B8 was studied systemically and in kidneys in a lapine model of endotoxin-induced disseminated intravascular coagulation (DIC). The increase in plasmatic PAI activity in the control group (n = 9) was inhibited in the MA-33B8 treated rabbits (n = 5). Control rabbits showed renal fibrin deposits, whereas only one of the MA-33B8 rabbits did so. These results were confirmed immunohistochemically in kidneys as PAI-1 immunostaining was seen inside the glomeruli and larger vessels in the control group, whereas MA-33B8 rabbits showed a remarkable decrease, demonstrating that MA-33B8 successfully inhibited PAI-1 in the kidneys as well. Therefore evidence for the important role of PAI-1 in fibrin generation in endotoxin-induced DIC is presented, suggesting that strategies aiming at its reduction can be useful in this pathology.
Hemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain.
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R
Montes
P J
PJ
Declerck
A
A
Calvo
M
M
Montes
J
J
Hermida
M C
MC
Muñoz
E
E
Rocha
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000628:therapy*; D005337:Fibrin / Q000378:metabolism*; D006487:Hemostasis / Q000187:drug effects; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000276:immunology* / Q000502:physiology; D011817:Rabbits
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D005337:Fibrin