Thromb Haemost 2015; 113(06): 1312-1322
DOI: 10.1160/TH14-09-0724
Blood Cells, Inflammation and Infection
Schattauer GmbH

Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation

Sofia Nordling
1   Department of Immunology, Genetics and Pathology, Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
,
Jaan Hong
1   Department of Immunology, Genetics and Pathology, Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
,
Karin Fromell
1   Department of Immunology, Genetics and Pathology, Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
,
Fredrik Edin
2   Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Uppsala University Hospital, Uppsala, Sweden
,
Johan Brännström
1   Department of Immunology, Genetics and Pathology, Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
,
Rolf Larsson
1   Department of Immunology, Genetics and Pathology, Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
,
Bo Nilsson
1   Department of Immunology, Genetics and Pathology, Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
,
Peetra U. Magnusson
1   Department of Immunology, Genetics and Pathology, Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
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Weitere Informationen

Publikationsverlauf

Received: 03. September 2014

Accepted after major revision: 09. Januar 2015

Publikationsdatum:
18. November 2017 (online)

Summary

Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vasculature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.

 
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