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CD39 Modulates Endothelial Cell Activation and Apoptosis

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Abstract

Background

CD39 is the dominant vascular nucleoside triphosphate diphosphohydrolase (NTPDase) that exerts major effects on platelet reactivity by the regulated hydrolysis of extracellular adenine nucleotides. The effects of NTPDases on endothelial cell (EC) activation and apoptosis remain unexplored.

Material and Methods

Recombinant replication-deficient adenoviruses were constructed with human CD39 cDNA (rAdCD39) or the bacterial β-galactosidase (rAdβgal).

Results

Intact human umbilical vein EC cultures infected with rAdCD39 had substantial and stable increases in NTPDase biochemical activity (14.50 ± 3.50 Pi nmole/well/min), when contrasted with noninfected cells (0.95 ± 0.002) and rAdβgal infected cells (1.01 ± 0.02; p <0.005). Increased NTPDase activity efficiently inhibited immediate type 2Y purinergic receptor (P2Y)-mediated EC activation responses viz. von Willebrand factor secretion in response to extracellular ATP. In addition, CD39 up-regulation blocked ATP-induced translocation of the transcription nuclear factor (NF)-κB to the cell nucleus, and abrogated transcription of mRNA encoding E-selectin, and consequent protein synthesis. CD39 also decreased the extent of apoptosis triggered by putative type-2X purinergic (P2X7) receptors in response to high concentrations of extracellular ATP in vitro.

Conclusion

These properties of CD39 indicate primary vascular protective effects with potential therapeutic applications.

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Acknowledgments

CG is a recipient of a fellowship from the Deutsche Forschungsgemeinschaft. This work was supported by NIH R01 HL57307 and American Heart Association Grant in Aid 9650490N. SCR also thanks the MRC UCT Liver Center, Cape Town, South Africa for early research support that facilitated the current work.

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Authors and Affiliations

  1. Center for Immunobiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Christian Goepfert, Masato Imai, Sophie Brouard, Eva Csizmadia, Elzbieta Kaczmarek &  Simon C. Robson

  2. Beth Israel Deaconess Medical Center, Rm. 370 H, Research North, 99 Brookline Avenue, Boston, MA, 02215, USA

    Simon C. Robson

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  1. Christian Goepfert
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  2. Masato Imai
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Correspondence to Simon C. Robson.

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Goepfert, C., Imai, M., Brouard, S. et al. CD39 Modulates Endothelial Cell Activation and Apoptosis. Mol Med 6, 591–603 (2000). https://doi.org/10.1007/BF03401797

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