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Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
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Published on: November 22, 2024

The immunomodulator FTY720 is phosphorylated and released from platelets.

Yoshihiro Anada1, Yasuyuki Igarashi, Akio Kihara

  • 1Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan.

European Journal of Pharmacology
|June 8, 2007
PubMed
Summary

Platelets efficiently convert the immunomodulator FTY720 into its active form, FTY720-phosphate (FTY720-P). This active compound is then released into circulation, suggesting platelets are a key source of plasma FTY720-P.

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Area of Science:

  • Immunology
  • Pharmacology
  • Hematology

Background:

  • The immunomodulator FTY720 sequesters lymphocytes in lymphoid tissues.
  • In vivo, FTY720 is converted to FTY720-phosphate (FTY720-P), which activates the sphingosine 1-phosphate receptor S1P(1).
  • The primary site of FTY720-P production remained unknown.

Purpose of the Study:

  • To investigate the cellular source of plasma FTY720-P.
  • To elucidate the mechanism of FTY720-P release from producing cells.

Main Methods:

  • Incubation of FTY720 with isolated human platelets.
  • Measurement of FTY720-P levels in platelet suspensions and supernatants.
  • Assessment of FTY720-P release under basal and stimulated conditions (thrombin).

Main Results:

  • Platelets efficiently phosphorylate FTY720 to FTY720-P.
  • FTY720-P is released into the extracellular space by platelets.
  • Release is largely independent of platelet activation but slightly enhanced by thrombin.
  • Evidence suggests involvement of two distinct transporters in FTY720-P efflux.

Conclusions:

  • Platelets are identified as a significant source of plasma FTY720-P.
  • Platelet-derived FTY720-P contributes to the systemic effects of FTY720.
  • Understanding FTY720-P transport mechanisms may offer therapeutic insights.