Prevention of Renal Fibrin Deposition in Endotoxin-induced DIC through Inhibition of PAI-1

Ramón Montes; Paul J. Declerck; Alfonso Calvo; Marta Montes; José Hermida; María C. Muñoz; Eduardo Rocha

doi:10.1055/s-0037-1613969

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(01): 65-70
DOI: 10.1055/s-0037-1613969

Commentary

Schattauer GmbH

Prevention of Renal Fibrin Deposition in Endotoxin-induced DIC through Inhibition of PAI-1

Authors

Ramón Montes

¹From the Hemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
Paul J. Declerck

²Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Belgium, Pamplona, Spain
Alfonso Calvo

³Histology Department, University of Navarra, Pamplona, Spain
Marta Montes

⁴Pathology Service, Hospital Virgen del Camino, Pamplona, Spain
José Hermida

¹From the Hemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
María C. Muñoz

¹From the Hemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
Eduardo Rocha

¹From the Hemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain

⁵Hematology Service, University Clinic of Navarra, Pamplona, Spain

Abstract

Summary

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.

Key words

PAI-1 - sepsis - endotoxemia - monoclonal antibodies - kidney

Full Text

References

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