PMID: 7542999Aug 1, 1995Paper

Immunoselective targeting of an anti-thrombin agent to the surface of cytokine-activated vascular endothelial cells

Arteriosclerosis, Thrombosis, and Vascular Biology
J M KielyM A Gimbrone

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

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Citations

Sep 26, 2008·Cell and Tissue Research·Eric SimoneVladimir Muzykantov
Aug 2, 1996·Atherosclerosis·E B Smith
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
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
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

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