Abstract
An immunoconjugate was designed to target hirudin, a potent and specific inhibitor of thrombin, to the surface of activated endothelial cells. Hirudin was covalently cross-linked to the monoclonal antibody H18/7 that recognizes the extracellular domain of E-selectin (CD62E), an endothelium-leukocyte adhesion molecule that is expressed only on cytokine-activated endothelium. The hirudin-H18/7 immunoconjugate selectively bound to interleukin-1-activated but not to unactivated cultured human umbilical vein endothelial cells with a temporal profile similar to that of inducible cell-surface procoagulant activity. When bound to activated endothelial cells, the hirudin-H18/7 immunoconjugate significantly inhibited endogenous thrombin activity generated from coincubated human plasma and fibrin clot formation on the monolayer surface. Cellular responses that are mediated via the thrombin receptor, such as increases in cytoskeletal F-actin content, also were significantly downregulated, and monolayers were protected from thrombin-induced disruption by this treatment. The ability to selectively antagonize thrombin-dependent processes at the endothelium-blood interface may provide new insights into complex pathophysiological processes, suc...Continue Reading
References
Oct 1, 1992·The Journal of Clinical Investigation·N A NelkenS R Coughlin
Jun 1, 1992·Thrombosis Research·P Chang, D L Aronson
Apr 1, 1990·Physiological Reviews·J S Pober, R S Cotran
Feb 1, 1991·Transplantation·D M BriscoeJ S Pober
Feb 25, 1991·Science·M I Cybulsky, M A Gimbrone
Jul 20, 1990·Science·T J RydelJ W Fenton
Mar 3, 1989·Science·M P BevilacquaB Seed
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M P BevilacquaM A Gimbrone
Jul 18, 1986·Cell·L A SpornD D Wagner
Oct 1, 1987·Seminars in Thrombosis and Hemostasis·M P Bevilacqua, M A Gimbrone
Jul 3, 1987·Cell·J H MorrisseyT S Edgington
Jan 1, 1987·Annals of the New York Academy of Sciences·M A Gimbrone
Jan 1, 1986·Annals of the New York Academy of Sciences·G A ZimmermanS M Prescott
Jul 1, 1986·Journal of Cellular Physiology·J G GarciaA B Malik
Dec 2, 1967·Nature·M G Davey, E F Lüscher
Aug 1, 1984·The Journal of Experimental Medicine·M P BevilacquaM A Gimbrone
May 13, 1983·Science·R Bar-ShavitJ W Fenton
Jan 1, 1994·Microvascular Research·G Thurston, D Turner
Jan 1, 1994·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·L A Harker
Citations
Sep 26, 2008·Cell and Tissue Research·Eric SimoneVladimir Muzykantov
Aug 2, 1996·Atherosclerosis·E B Smith
Jun 15, 2005·Biomaterials·A Omolola Eniola, Daniel A Hammer
Apr 19, 2002·Biomaterials·A Omolola EniolaDaniel A Hammer
Mar 6, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·A Omolola Eniola, Daniel A Hammer
Aug 16, 2011·ACS Nano·Vladimir V ShuvaevVladimir R Muzykantov
May 22, 2010·Seminars in Thrombosis and Hemostasis·Ronald CarnemollaVladimir R Muzykantov
Oct 9, 1999·Transplantation·D ChenA Dorling
Sep 8, 2005·Blood·Bi-Sen DingVladimir R Muzykantov
Jul 2, 1998·Clinical and Experimental Immunology·D C IrelandD P de Bono
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·D D SpraggM A Gimbrone
Nov 15, 2014·Expert Opinion on Drug Delivery·Jacob S BrennerVladimir Muzykantov
Mar 24, 2016·Nanomedicine·Yan Teck HoJames Chen Yong Kah
Jun 27, 2013·Blood·Colin F GreinederVladimir R Muzykantov
Nov 22, 2005·Expert Opinion on Drug Delivery·Vladimir R Muzykantov
May 6, 2004·Blood·Daxin ChenAnthony Dorling
Jul 10, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Melpo Christofidou-SolomidouVladimir R Muzykantov
Dec 29, 2017·Drug Delivery and Translational Research·Raisa Yu KiselevaVladimir R Muzykantov
Jun 25, 2020·Advanced Drug Delivery Reviews·Patrick M GlassmanVladimir R Muzykantov