Academic Journal
Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes
| العنوان: | Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes |
|---|---|
| المؤلفون: | Alessandra Balduini, Christian Andrea Di Buduo, Alessandro Malara, Anna Lecchi, Paola Rebuzzini, Manuela Currao, Isabella Pallotta, Joseph A. Jakubowski, Marco Cattaneo |
| المصدر: | Haematologica, Vol 97, Iss 11 (2012) |
| بيانات النشر: | Ferrata Storti Foundation, 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Background The interaction of adenosine diphosphate with its P2Y1 and P2Y12 receptors on platelets is important for platelet function. However, nothing is known about adenosine diphosphate and its function in human megakaryocytes.Design and Methods We studied the role of adenosine diphosphate and P2Y receptors on proplatelet formation by human megakaryocytes in culture.Results Megakaryocytes expressed all the known eight subtypes of P2Y receptors, and constitutively released adenosine diphosphate. Proplatelet formation was inhibited by the adenosine diphosphate scavengers apyrase and CP/CPK by 60-70% and by the P2Y12 inhibitors cangrelor and 2-MeSAMP by 50-60%, but was not inhibited by the P2Y1 inhibitor MRS 2179. However, the active metabolites of the anti-P2Y12 drugs, clopidogrel and prasugrel, did not inhibit proplatelet formation. Since cangrelor and 2-MeSAMP also interact with P2Y13, we hypothesized that P2Y13, rather than P2Y12 is involved in adenosine diphosphate-regulated proplatelet formation. The specific P2Y13 inhibitor MRS 2211 inhibited proplatelet formation in a concentration-dependent manner. Megakaryocytes from a patient with severe congenital P2Y12 deficiency showed normal proplatelet formation, which was inhibited by apyrase, cangrelor or MRS 2211 by 50-60%. The platelet count of patients with congenital delta-storage pool deficiency, who lack secretable adenosine diphosphate, was significantly lower than that of patients with other platelet function disorders, confirming the important role of secretable adenosine diphosphate in platelet formation.Conclusions This is the first demonstration that adenosine diphosphate released by megakaryocytes regulates their function by interacting with P2Y13. The clinical relevance of this not previously described physiological role of adenosine diphosphate and P2Y13 requires further exploration. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/6463; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2011.059212 |
| URL الوصول: | https://doaj.org/article/59d53b63d88a40829f93546db5a197b1 |
| رقم الانضمام: | edsdoj.59d53b63d88a40829f93546db5a197b1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
|---|---|
| DOI: | 10.3324/haematol.2011.059212 |