Quantitative evaluation of the loss of human platelet dense bodies following stimulation by thrombin or A23187.

Costa, Jonathan L.; Detwiler, Thomas C.; Feinman, Richard D.; Murphy, Dennis L.; Patlak, Clifford S.; Pettigrew, Karen D.

doi:10.1113/jphysiol.1977.sp011669

Cited by 34 publications

(12 citation statements)

References 7 publications

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“…Consistent with this expression of the alpha granule protein P-selectin expression was the same in wild-type and HPS3 −/− platelets after maximal cell activation by calcium ionophore (Fig. 1G) or by thrombin receptor peptide and calcium ionophore, which are known to induce maximal platelet secretion (not shown) 23. However, leukocyte-platelet interactions were reduced in HPS3 −/− mice when compared to wild-type mice (Fig.…”

Section: Resultssupporting

confidence: 76%

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

et al. 2009

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Background— Platelet aggregation plays a critical role in myocardial infarction and stroke; however, the role of platelet secretion in atherosclerotic vascular disease is poorly understood. Therefore, we examined the hypothesis that platelet dense-granule secretion modulates thrombosis, inflammation, and atherosclerotic vascular remodeling after injury. Methods and Results— Functional deletion of the Hermansky-Pudlak syndrome 3 gene (HPS3 −/− ) markedly reduces platelet dense-granule secretion. HPS3 −/− mice have normal platelet counts, platelet morphology, and α-granule number, as well as maximal secretion of the α-granule marker P-selectin; however, their capacity to form platelet-leukocyte aggregates is significantly reduced ( P <0.05). To examine the role of platelet dense-granule secretion in these processes, atherosclerosis-prone mice with combined genetic deficiency of apolipoprotein E and HPS3 (ApoE −/− , HPS3 −/− ) were compared with congenic, atherosclerosis-prone mice with normal platelet secretion (ApoE −/− , HPS3 +/+ ). After 16 to 18 weeks on a high-fat diet, both groups of mice had similar fasting cholesterol levels and body weight. Carotid arteries of ApoE −/− , HPS3 +/+ mice thrombosed rapidly after FeCl 3 injury, but ApoE −/− , HPS3 −/− mice were completely resistant to thrombotic arterial occlusion ( P <0.01). Three weeks after injury, neointimal hyperplasia (from α-smooth muscle actin–positive cells) was significantly less ( P <0.001) in arteries from ApoE −/− , HPS3 −/− mice. In ApoE −/− , HPS3 −/− mice, there were also pronounced reductions in arterial inflammation, as indicated by a 74% decrease in CD45-positive leukocytes ( P <0.01) and a 73% decrease in Mac-3–positive macrophages ( P <0.05). Conclusions— In atherosclerotic mice, reduced platelet dense-granule secretion is associated with marked protection against the development of arterial thrombosis, inflammation, and neointimal hyperplasia after vascular injury.

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Section: Resultssupporting

confidence: 76%

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

et al. 2009

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“…We can estimate the concentration of polyP in the dense granule from the total amount of polyP in the whole platelet (see above). If we assume that the polyP in the dense granule is ϳ60% of the total (as it occurs with calcium, ADP, ATP, and PP i) , the volume of each granule is 0.1% platelet volume (9) and there is an average of 5 dense granules/platelet (8,28), the intragranular concentration of polyP is ϳ130 mM.…”

Section: Elemental Analysis and Isolation Of Human Platelet Densementioning

confidence: 99%

Human Platelet Dense Granules Contain Polyphosphate and Are Similar to Acidocalcisomes of Bacteria and Unicellular Eukaryotes

Ruiz

Lea

Oldfield

et al. 2004

Journal of Biological Chemistry

404

513

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Inorganic polyphosphate (polyP) has been identified and measured in human platelets. Millimolar levels (in terms of P i residues) of short chain polyP were found. The presence of polyP of ϳ70 -75 phosphate units was identified by 31 P NMR and by urea-polyacrylamide gel electrophoresis of platelet extracts. An analysis of human platelet dense granules, purified using metrizamide gradient centrifugation, indicated that polyP was preferentially located in these organelles. This was confirmed by visualization of polyP in the dense granules using 4,6-diamidino-2-phenylindole and by its release together with pyrophosphate and serotonin upon thrombin stimulation of intact platelets. Dense granules were also shown to contain large amounts of calcium and potassium and both bafilomycin A 1 -sensitive ATPase and pyrophosphatase activities. In agreement with these results, when human platelets were loaded with the fluorescent calcium indicator Fura-2 acetoxymethyl ester to measure their intracellular Ca and 2) the effect of ionomycin, which could not take Ca 2؉ out of acidic organelles and was more effective after alkalinization of this compartment by the previous addition of nigericin, monensin, or NH 4 Cl. All of these characteristics of the platelet dense granules, together with their known acidity and high density (both by weight and by electron microscopy), are similar to those of acidocalcisomes (volutin granules, polyP bodies) of bacteria and unicellular eukaryotes. The results suggest that acidocalcisomes have been conserved during evolution from bacteria to humans.

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“…The dense body content of fresh and previously frozen platelets was quantitated using transmission electron microscopy [3]; to avoid a technical problem The recipient's blood volume was calculated from the red cell volume measured with 51Cr-labeled autol ogous red cells and the total body hematocrit, or was estimated from the patient's body surface area [28].…”

Section: In Vitro Platelet Function Studiesmentioning

confidence: 99%

Cryopreservation of Human Platelets Using 6% Dimethyl Sulfoxide and Storage at -80°C

Meleragno¹,

Carciero²,

Feingold³

et al. 1985

Vox Sanguinis

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Platelet studies were done in healthy male volunteers and in thrombocytopenic patients. Some of the platelets used in the study were isolated by mechanical apheresis using either the Haemonetics blood processor 30, the IBM blood processor 2997 or the Fenwal CS-3000 blood processor before freezing. Other platelets were isolated from individual units of whole blood and pooled before freezing. The platelets were frozen with a 6% cryoprotectant (DMSO) in a polyvinylchloride (PVC) plastic bag or a polyolefin plastic bag at -80°C in a mechanical freezer and stored for as long as 3 years. Some of the frozen platelets were transported in dry ice in polystyrene foam containers to determine whether they would be adversely affected by such treatment. Platelet recovery after freezing, thawing and washing was about 75%. In the healthy male volunteers, in vivo recovery of autologous platelets 1 - 2 h after transfusion was about 33%, and the life span was about 8 days. In the thrombocytopenic patients, in vivo recovery values were 50% of those from fresh platelets. The transfusion of previously frozen washed platelets reduced clinical bleeding in the thrombocytopenic patients with bleeding. There was no evidence of quality deterioration in platelets after storage at -80°C for at least 2 years, as determined from in vitro recovery and in vivo survival values, nor was there any adverse effect as a result of shipment of the frozen platelets in dry ice in polystyrene foam containers from one facility to another.

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Quantitative evaluation of the loss of human platelet dense bodies following stimulation by thrombin or A23187.

Cited by 34 publications

References 7 publications

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

Human Platelet Dense Granules Contain Polyphosphate and Are Similar to Acidocalcisomes of Bacteria and Unicellular Eukaryotes

Cryopreservation of Human Platelets Using 6% Dimethyl Sulfoxide and Storage at -80°C

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