CD39 is incorporated into plasma microparticles where it maintains functional properties and impacts endothelial activation.
Plasma microparticles (MPs, <1.5 mum) originate from platelet and cell membrane lipid rafts and possibly regulate inflammatory responses and thrombogenesis. These actions are mediated through their phospholipid-rich surfaces and associated cell-derived surface molecules. The ectonucleotidase CD39/ecto-nucleoside triphosphate diphosphohydrolase1 (E-NTPDase1) modulates purinergic signalling through pericellular ATP and ADP phosphohydrolysis and is localized within lipid rafts in the membranes of endothelial- and immune cells. This study aimed to determine whether CD39 associates with circulating MPs and might further impact phenotype and function. Plasma MPs were found to express CD39 and exhibited classic E-NTPDase ecto-enzymatic activity. Entpd1 (Cd39) deletion in mice produced a pro-inflammatory phenotype associated with quantitative and qualitative differences in the MP populations, as determined by two dimensional-gel electrophoresis, western blot and flow cytometry. Entpd1-null MPs were also more abundant, had significantly higher proportions of platelet- and endothelial-derived elements and decreased levels of interleukin-10, tumour necrosis factor receptor 1 and matrix metalloproteinase 2. Consequently, Cd39-null MP augment endothelial activation, as determined by inflammatory cytokine release and upregulation of adhesion molecules in vitro. In conclusion, CD39 associates with circulating MP and may directly or indirectly confer functional properties. Our data also suggest a modulatory role for CD39 within MP in the exchange of regulatory signals between leucocytes and vascular cells.
Liver Center, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA 02215, USA.
Yara
Y
Banz
Guido
G
Beldi
Yan
Y
Wu
Ben
B
Atkinson
Anny
A
Usheva
Simon C
SC
Robson
D000251:Adenosine Triphosphatases / Q000032:analysis*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008832:Microchemistry / Q000379:methods; D010949:Plasma / Q000737:chemistry* / Q000201:enzymology; D022142:Secretory Vesicles / Q000737:chemistry
D015703:Antigens, CD; D001798:Blood Proteins; D016207:Cytokines; D045726:Metalloproteases; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D001081:Apyrase; C067869:CD39 antigen