| Autor: |
Kiran Gotru S; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., van Geffen JP; Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands., Nagy M; Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands., Mammadova-Bach E; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Eilenberger J; Practice for Pediatric Hematology and Hemostaseology, Munich, Germany., Volz J; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Manukjan G; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Schulze H; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Wagner L; Medical Clinic and Policlinic II, Division of Hepatology, University Hospital Würzburg, Würzburg, Germany., Eber S; Practice for Pediatric Hematology and Hemostaseology, Munich, Germany., Schambeck C; Haemostasikum, Munich, Germany., Deppermann C; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Brouns S; Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands., Nurden P; Institut Hospitalo-Universitaire LIRYC, Plateforme Technologique d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France., Greinacher A; Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany., Sachs U; Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany., Nieswandt B; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Hermanns HM; Medical Clinic and Policlinic II, Division of Hepatology, University Hospital Würzburg, Würzburg, Germany., Heemskerk JWM; Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands., Braun A; Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany. attila.braun@virchow.uni-wuerzburg.de. |
| Abstrakt: |
Zinc (Zn 2+ ) can modulate platelet and coagulation activation pathways, including fibrin formation. Here, we studied the (patho)physiological consequences of abnormal platelet Zn 2+ storage and release. To visualize Zn 2+ storage in human and mouse platelets, the Zn 2+ specific fluorescent dye FluoZin3 was used. In resting platelets, the dye transiently accumulated into distinct cytosolic puncta, which were lost upon platelet activation. Platelets isolated from Unc13d -/- mice, characterized by combined defects of α/δ granular release, showed a markedly impaired Zn 2+ release upon activation. Platelets from Nbeal2 -/- mice mimicking Gray platelet syndrome (GPS), characterized by primarily loss of the α-granule content, had strongly reduced Zn 2+ levels, which was also confirmed in primary megakaryocytes. In human platelets isolated from patients with GPS, Hermansky-Pudlak Syndrome (HPS) and Storage Pool Disease (SPD) altered Zn 2+ homeostasis was detected. In turbidity and flow based assays, platelet-dependent fibrin formation was impaired in both Nbeal2 -/- and Unc13d -/- mice, and the impairment could be partially restored by extracellular Zn 2+ . Altogether, we conclude that the release of ionic Zn 2+ store from secretory granules upon platelet activation contributes to the procoagulant role of Zn 2+ in platelet-dependent fibrin formation. |
