title: Disordered cellular migration and angiogenesis in cd39-null mice.
abstract: BACKGROUND
  Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 is the major ectonucleotidase of endothelial cells and monocytes and catalyzes phosphohydrolysis of extracellular nucleoside diphosphates (NDP) and triphosphates (NTP, eg, ATP and UTP). Deletion of cd39 causes perturbations in the hydrolysis of NTP and NDP in the vasculature. Activation of P2 receptors appears to influence endothelial cell chemotactic and mitogenic responses in vitro. Therefore, aberrant regulation of nucleotide P2 receptors may influence angiogenesis in cd39-null mice. Methods and Results- In control mice, implanted Matrigel plugs containing growth factors were rapidly populated by monocyte/macrophages, endothelial cells, and pericytes, with the development of new vessels over days. In cd39-null mice, migrating cells were completely confined to the tissue-Matrigel interface in a clearly stratified manner. Absolute failure of new vessel ingrowth was consistently observed in the mutant mice. Linked to these findings, chemotaxis of cd39-null monocyte/macrophages to nucleotides was impaired in vitro. This abnormality was associated with desensitization of nucleotide receptor P2Y-mediated signaling pathways.
  
  
  CONCLUSIONS
  Our findings demonstrate a role for NTPDase1 and phosphohydrolysis of extracellular nucleotides in the regulation of the cellular infiltration and new vessel growth in a model of angiogenesis.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: C
authors.initials: C
authors.lastname: Goepfert
authors.forename: C
authors.initials: C
authors.lastname: Sundberg
authors.forename: J
authors.initials: J
authors.lastname: Sévigny
authors.forename: K
authors.initials: K
authors.lastname: Enjyoji
authors.forename: T
authors.initials: T
authors.lastname: Hoshi
authors.forename: E
authors.initials: E
authors.lastname: Csizmadia
authors.forename: S
authors.initials: S
authors.lastname: Robson
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000032:analysis; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D001081:Apyrase; D001808:Blood Vessels / Q000737:chemistry / Q000254:growth & development; D002465:Cell Movement / Q000502:physiology*; D018932:Chemokine CCL2 / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D039661:Integrin beta3; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000502:physiology*; D043583:Nucleoside-Triphosphatase; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011509:Proteoglycans / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D012701:Serotonin / Q000494:pharmacology; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D017766:Acid Anhydride Hydrolases; D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate; D000941:Antigens; D015703:Antigens, CD; D001081:Apyrase; D018932:Chemokine CCL2; D039661:Integrin beta3; D043583:Nucleoside-Triphosphatase; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; D011509:Proteoglycans; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017978:Receptors, Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D012701:Serotonin; D000099216:Chondroitin Sulfate Proteoglycan 4; C067869:CD39 antigen