CD39 modulates endothelial cell activation and apoptosis.
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.


METHODS
Recombinant replication-deficient adenoviruses were constructed with human CD39 cDNA (rAdCD39) or the bacterial beta-galactosidase (rAdbetagal).


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 rAdbetagal 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)-kappaB 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.


CONCLUSIONS
These properties of CD39 indicate primary vascular protective effects with potential therapeutic applications.
Goepfert
C
C
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Imai
M
M
Brouard
S
S
Csizmadia
E
E
Kaczmarek
E
E
Robson
S C
SC
D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001081:Apyrase / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins; D020302:Weibel-Palade Bodies / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D019040:E-Selectin; D006490:Hemostatics; D016328:NF-kappa B; D012333:RNA, Messenger; D014841:von Willebrand Factor; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D013917:Thrombin; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen