Decreased sickle red blood cell adhesion to laminin by hydroxyurea is associated with inhibition of Lu/BCAM protein phosphorylation
| Autor: | Vicky Chaar, Julien Picot, Yves Colin, Pablo Bartolucci, Christine Fauroux, Dora Bachir, Wassim El Nemer, Anoosha Habibi, Frédéric Galactéros, Caroline Le Van Kim |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Immunology Erythrocytes Abnormal Anemia Sickle Cell Biochemistry Blood cell 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine BCAM Laminin hemic and lymphatic diseases Internal medicine medicine Cell Adhesion Cyclic AMP Humans Hydroxyurea Cyclic adenosine monophosphate Phosphorylation Cell adhesion Protein kinase A 030304 developmental biology 0303 health sciences biology Cell adhesion molecule Cell Biology Hematology Lutheran Blood-Group System 3. Good health Cell biology Endocrinology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis biology.protein K562 Cells Cell Adhesion Molecules Intracellular |
| Zdroj: | Blood. 116(12) |
| ISSN: | 1528-0020 |
| Popis: | 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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