title: CD39 modulates IL-1 release from activated endothelial cells.
abstract: The activation of endothelial cells (EC) and monocyte-macrophages (M&phi;) by lipopolysaccharide (LPS) is considered an important element of the vascular injury observed in endotoxemia. Interleukin-1 (IL-1) beta release from M&phi; in response to LPS, appears to be mediated by the autocrine/paracrine release of ATP via P2X7 receptor activation. In EC, similar nucleotide-mediated signaling pathways may be influenced by high levels of expression of CD39, the vascular nucleoside triphosphate diphosphohydrolase (NTPDase; ENTPD I). To determine whether CD39 modulates ATP-mediated release of IL-1 from EC, we stimulated human EC with LPS and measured levels of ATP secretion and IL-1 release. LPS triggered ATP secretion from EC that was soon followed by IL-1alpha release. Overexpression of CD39 following infection with recombinant CD39 adenoviral vectors (AdCD39) abrogated the initial phase of ATP secretion and inhibited IL-1alpha release; comparable results were obtained with soluble NTPDase. These data demonstrate that CD39/NTPDase modulates IL-1alpha release from LPS stimulated human EC.
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: M
authors.initials: M
authors.lastname: Imai
authors.forename: C
authors.initials: C
authors.lastname: Goepfert
authors.forename: E
authors.initials: E
authors.lastname: Kaczmarek
authors.forename: S C
authors.initials: SC
authors.lastname: Robson
mesh_terms: D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology*; D019446:Endotoxemia / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen