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Thromb Haemost 2006; 96(06): 802-806
DOI: 10.1160/TH06-07-0418
Wound Healing and Inflammation/Infection
Schattauer GmbH

A non-anticoagulant synthetic pentasaccharide reduces inflammation in a murine model of kidney ischemia-reperfusion injury

Rolf Dario Frank
1   Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
2   Department of Nephrology, University Hospital RWTH Aachen, Aachen, Germany
,
Todd Holscher
1   Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
,
Gernot Schabbauer
1   Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
,
Michael Tencati
1   Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
,
Rafal Pawlinski
1   Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
,
Jeffrey I. Weitz
3   Departments of Medicine and Biochemistry, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
,
Nigel Mackman
1   Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
› Author Affiliations
Further Information

Publication History

Received 31 July 2006

Accepted after resubmission 12 October 2006

Publication Date:
29 November 2017 (online)

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Summary

Fondaparinux is a synthetic pentasaccharide that selectively inhibits factor Xa (FXa) in an antithrombin-dependent fashion.This newly developed anticoagulant is used in the prevention and treatment of venous thromboembolism. Recently, we showed that fondaparinux reduces inflammation and protects the kidney from ischemia-reperfusion (I/R) injury. However, the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection is unknown.To address this, we chemically modified fondaparinux to abolish its affinity for antithrombin and analyzed the effect of this non-anti- coagulant (NAC)-pentasaccharide on binding of U937 cells to P-selectin in vitro and on inflammation in a murine model of kidney I/R injury. NAC-pentasaccharide was as effective as fondaparinux at inhibiting the binding of U937 cells to P-selectin.In addition, NAC-pentasaccharide significantly reduced IL-6 and MIP-2 expression and injury in the kidney I/R model.These findings indicate that the anti-inflammatory activity of fondaparinux can be dissociated from its anticoagulant activity and that NACpentasaccharide is protective in kidney I/R injury.

Keywords

Anticoagulant - inflammation - animal model - ischemia-reperfusion injury
 

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