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Simon C. Robson^*,, Elzbieta Kaczmarek^*, Jonathan B. Siegel^*, Daniel Candinas^*, Katarzyna Koziak^*, Maria Millan^*, Wayne W. Hancock^*, and Fritz H. Bach^*

From the ^* Sandoz Center for Immunobiology and Departments of Medicine, Pathology and Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215; and Medical Research Council, University of Cape Town Liver Center, Medical School, Groote Schuur Hospital, Observatory, Cape Town 7925

Quiescent endothelial cells (EC) regulate blood flow and prevent intravascular thrombosis. This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines. Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature. An additional thromboregulatory factor, ATP diphosphohydrolase (ATPDase; designated as EC 3.6.1.5) is also expressed by quiescent EC, and has the capacity to degrade the extracellular inflammatory mediators ATP and ADP to AMP, thereby inhibiting platelet activation and modulating vascular thrombosis. We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo. Because platelet activation and aggregation are important components of the hemostatic changes that accompany inflammatory diseases, we suggest that the loss of vascular ATPDase may be crucial for the progression of vascular injury.

Research work was supported by Sandoz Pharma (Basel, Switzerland).

¹Abbreviations used in this paper: ATPDase, ATP diphosphohydrolase; EC, endothelial cells; FBS, fetal bovine serum; hEC, human aortic EC; HRP, horseradish peroxidase; HUVEC, human umbilical vein EC; NO, nitric oxide; PAF, platelet activation factor; pEC, pig aortic EC; SOD, superoxide dismutase.

This work was presented (in part) at the Third International Congress on Xenotransplantation in Boston, MA, September 27–October 1, 1995.

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