Journal article
Authors list: Gotru, Sanjeev Kiran; van Geffen, Johanna P.; Nagy, Magdolna; Mammadova-Bach, Elmina; Eilenberger, Julia; Volz, Julia; Manukjan, Georgi; Schulze, Harald; Wagner, Leonard; Eber, Stefan; Schambeck, Christian; Deppermann, Carsten; Brouns, Sanne; Nurden, Paquita; Greinacher, Andreas; Sachs, Ulrich; Nieswandt, Bernhard; Hermanns, Heike M.; Heemskerk, Johan W. M.; Braun, Attila
Publication year: 2019
Journal: Scientific Reports
Volume number: 9
ISSN: 2045-2322
Open access status: Gold
DOI Link: https://doi.org/10.1038/s41598-019-44751-w
Publisher: Nature Research
Abstract:
Zinc (Zn2+) can modulate platelet and coagulation activation pathways, including fibrin formation. Here, we studied the (patho)physiological consequences of abnormal platelet Zn2+ storage and release. To visualize Zn2+ storage in human and mouse platelets, the Zn2+ 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 alpha/delta granular release, showed a markedly impaired Zn2+ release upon activation. Platelets from Nbeal2(-/-) mice mimicking Gray platelet syndrome (GPS), characterized by primarily loss of the alpha-granule content, had strongly reduced Zn2+ 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 Zn2+ 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 Zn2+. Altogether, we conclude that the release of ionic Zn2+ store from secretory granules upon platelet activation contributes to the procoagulant role of Zn2+ in platelet-dependent fibrin formation.
Citation Styles
Harvard Citation style: Gotru, S., van Geffen, J., Nagy, M., Mammadova-Bach, E., Eilenberger, J., Volz, J., et al. (2019) Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases, Scientific Reports, 9, Article 8333. https://doi.org/10.1038/s41598-019-44751-w
APA Citation style: Gotru, S., van Geffen, J., Nagy, M., Mammadova-Bach, E., Eilenberger, J., Volz, J., Manukjan, G., Schulze, H., Wagner, L., Eber, S., Schambeck, C., Deppermann, C., Brouns, S., Nurden, P., Greinacher, A., Sachs, U., Nieswandt, B., Hermanns, H., Heemskerk, J., ...Braun, A. (2019). Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases. Scientific Reports. 9, Article 8333. https://doi.org/10.1038/s41598-019-44751-w
Keywords
HEMOSTASIS; NBEAL2
