Publication Date:
2014-11-16
Description:
Sphingosine 1-phosphate (S1P) is a powerful regulator of platelet formation. Enzymes generating S1P include sphingosine kinase 1. The present study thus explored the role of sphingosine kinase 1 in platelet formation and function. Activation-dependent platelet integrin α IIb β 3 activation and secretion of platelets lacking functional sphingosine kinase 1 ( sphk1 –/– ) and of wild-type platelets ( sphk1 +/+ ) were determined utilizing flow cytometry and chronolume luciferin assay. Cytosolic Ca 2+ activity ([Ca 2+ ] i ) and aggregation were measured using fura-2 fluorescence and aggregometry, respectively. In vitro platelet adhesion and thrombus formation were evaluated using a flow chamber with shear rates of 1,700 s –1 . Activation-dependent increase of [Ca 2+ ] i , degranulation (release of alpha and dense granules), integrin α IIb β 3 activation, and aggregation were all significantly increased in sphk1 –/– platelets compared with sphk1 +/+ platelets. Moreover, while platelet adhesion and thrombus formation under arterial shear rates were significantly augmented in Sphk1-deficient platelets, bleeding time and blood count were unaffected in sphk1 –/– mice. In conclusion, sphingosine kinase 1 is a powerful negative regulator of platelet function counteracting degranulation, aggregation, and thrombus formation.
Print ISSN:
0363-6143
Electronic ISSN:
1522-1563
Topics:
Medicine
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