A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation.
We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sial...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2011
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| _version_ | 1797097360380133376 |
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| author | Jones, C Denecke, J Sträter, R Stölting, T Schunicht, Y Zeuschner, D Klumperman, J Lefeber, D Spelten, O Zarbock, A Kelm, S Strenge, K Haslam, S Lühn, K Stahl, D Gentile, L Schreiter, T Hilgard, P Beck-Sickinger, A Marquardt, T Wild, M |
| author_facet | Jones, C Denecke, J Sträter, R Stölting, T Schunicht, Y Zeuschner, D Klumperman, J Lefeber, D Spelten, O Zarbock, A Kelm, S Strenge, K Haslam, S Lühn, K Stahl, D Gentile, L Schreiter, T Hilgard, P Beck-Sickinger, A Marquardt, T Wild, M |
| author_sort | Jones, C |
| collection | OXFORD |
| description | We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of α2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected. |
| first_indexed | 2024-03-07T04:54:26Z |
| format | Journal article |
| id | oxford-uuid:d61a49b9-9a41-4023-9dce-b9f3362556dc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:54:26Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:d61a49b9-9a41-4023-9dce-b9f3362556dc2022-03-27T08:30:57ZA novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d61a49b9-9a41-4023-9dce-b9f3362556dcEnglishSymplectic Elements at Oxford2011Jones, CDenecke, JSträter, RStölting, TSchunicht, YZeuschner, DKlumperman, JLefeber, DSpelten, OZarbock, AKelm, SStrenge, KHaslam, SLühn, KStahl, DGentile, LSchreiter, THilgard, PBeck-Sickinger, AMarquardt, TWild, MWe describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of α2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected. |
| spellingShingle | Jones, C Denecke, J Sträter, R Stölting, T Schunicht, Y Zeuschner, D Klumperman, J Lefeber, D Spelten, O Zarbock, A Kelm, S Strenge, K Haslam, S Lühn, K Stahl, D Gentile, L Schreiter, T Hilgard, P Beck-Sickinger, A Marquardt, T Wild, M A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation. |
| title | A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation. |
| title_full | A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation. |
| title_fullStr | A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation. |
| title_full_unstemmed | A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation. |
| title_short | A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation. |
| title_sort | novel type of macrothrombocytopenia associated with a defect in α2 3 sialylation |
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