Platelet secretion is kinetically heterogeneous in an agonist-responsive manner

Deepa Jonnalagadda, Leighton T Izu, Sidney W. Whiteheart

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Platelets release numerous bioactive molecules stored in their granules enabling them to exert a wide range of effects on the vascular microenvironment. Are these granule cargo released thematically in a context-specific pattern or via a stochastic, kinetically controlled process? Here we sought to describe the platelet exocytosis using a systematic examination of platelet secretion kinetics. Platelets were stimulated for increasing times with different agonists (ie, thrombin, PAR1-agonist, PAR4-agonist, and convulxin) and micro-ELISA arrays were used to quantify the release of 28 distinct α-granule cargo molecules. Agonist potency directly correlated with the speed and extent of release. PAR4-agonist induced slower release of fewer molecules, whereas thrombin rapidly induced the greatest release. Cargo with opposing actions (eg, proangiogenic and antiangiogenic) had similar release profiles, suggesting limited thematic response to specific agonists. From the release time-course data, rate constants were calculated and used to probe for underlying patterns. Probability density function and operator variance analyses were consistent with 3 classes of release events, differing in their rates. The distribution of cargo into these 3 classes was heterogeneous, suggesting that platelet secretion is a stochastic process potentially controlled by several factors, such as cargo solubility, granule shape, and/or granule-plasma membrane fusion routes.

Original languageEnglish (US)
Pages (from-to)5209-5216
Number of pages8
JournalBlood
Volume120
Issue number26
DOIs
StatePublished - Dec 20 2012

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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