Disordered cellular migration and angiogenesis in cd39-null mice
| Autor: | Tomokazu Hoshi, Christian Goepfert, Eva Csizmadia, Simon C. Robson, Keiichi Enjyoji, Christian Sundberg, Jean Sévigny |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Angiogenesis Monocytes chemistry.chemical_compound Mice Adenosine Triphosphate Cell Movement Receptor Chemokine CCL2 Adenosine Triphosphatases Mice Knockout Apyrase Integrin beta3 Cell migration Drug Synergism Nucleoside-Triphosphatase Immunohistochemistry Cell biology Acid Anhydride Hydrolases Endothelial stem cell Platelet Endothelial Cell Adhesion Molecule-1 medicine.anatomical_structure Biochemistry Nucleoside triphosphate Female Proteoglycans Cardiology and Cardiovascular Medicine Serotonin Endothelium Genotype Neovascularization Physiologic Mice Inbred Strains Platelet Membrane Glycoproteins Biology Receptor Platelet-Derived Growth Factor beta Antigens CD Physiology (medical) medicine Animals Receptors Growth Factor Antigens Matrigel Monocyte Macrophages Receptor Protein-Tyrosine Kinases Mice Inbred C57BL Receptors Vascular Endothelial Growth Factor chemistry Mutation Blood Vessels |
| Zdroj: | Circulation. 104(25) |
| ISSN: | 1524-4539 |
| Popis: | 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 ofcd39causes 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 incd39-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. Incd39-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 ofcd39-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. |
| Databáze: | OpenAIRE |
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