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Defective Zn
- Source :
- Scientific Reports
- Publication Year :
- 2018
-
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 α/δ 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 α-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.
- Subjects :
- inorganic chemicals
Adult
Blood Platelets
Male
Platelet Storage Pool Deficiency
Adolescent
Gray Platelet Syndrome
Article
Mice
Cytosol
Nephelometry and Turbidimetry
Animals
Homeostasis
Humans
Child
Blood Coagulation
Mice, Knockout
Fibrin
Microscopy, Confocal
Membrane Proteins
Blood Proteins
Platelet Activation
Healthy Volunteers
Coagulation system
Zinc
Microscopy, Fluorescence
Hermanski-Pudlak Syndrome
Metals
biological sciences
health occupations
bacteria
Female
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.pmid..........219452f9fc6fba668e10c9ccf406bb37