| First Author | Kiran Gotru S | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 8333 |
| PubMed ID | 31171812 | Mgi Jnum | J:281224 |
| Mgi Id | MGI:6357285 | Doi | 10.1038/s41598-019-44751-w |
| Citation | Kiran Gotru S, et al. (2019) Defective Zn(2+) homeostasis in mouse and human platelets with alpha- and delta-storage pool diseases. Sci Rep 9(1):8333 |
| abstractText | 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 alpha/delta 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 alpha-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. |
