Decreased sickle red blood cell adhesion to laminin by hydroxyurea is associated with inhibition of Lu/BCAM protein phosphorylation
| Autor: | Bartolucci, Pablo, Chaar, Vicky, Picot, Julien, Bachir, Dora, Habibi, Anoosha, Fauroux, Christine, Galactéros, Frédéric, Colin, Yves, Le Van Kim, Caroline, El Nemer, Wassim |
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| Přispěvatelé: | Protéines de la membrane érythrocytaire et homologues non-érythroides, Université des Antilles et de la Guyane (UAG)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité des Maladies Génétiques du Globule Rouge, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), The investigation was supported by the Institut National de la Transfusion Sanguine (INTS), the Institut National de la Santé et de la Recherche Médicale (INSERM), a grant from the Agence Nationale de la Recherche (ANR, SCADHESION 2007), a grant from Région Île-de-France (SESAME 2007 no. F-08-1104/R) and a fellowship 'maladies rares' from the Société Française de Médecine Interne (SNFMI) and Actélion. |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
MESH: Erythrocytes
Abnormal MESH: K562 Cells MESH: Humans MESH: Lutheran Blood-Group System MESH: Phosphorylation hemic and lymphatic diseases MESH: Cell Adhesion Molecules MESH: Laminin [SDV.BC]Life Sciences [q-bio]/Cellular Biology MESH: Anemia Sickle Cell MESH: Hydroxyurea MESH: Cyclic AMP MESH: Cell Adhesion |
| Zdroj: | Blood Blood, American Society of Hematology, 2010, 116 (12), pp.2152-9. ⟨10.1182/blood-2009-12-257444⟩ |
| ISSN: | 0006-4971 1528-0020 |
| Popis: | International audience; Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vessel-wall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyurea-treated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level. |
| Databáze: | OpenAIRE |
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