Salicylate inhibits thrombopoiesis in rat megakaryocytes by changing the membrane micro-architecture

Itsuro Kazama, Asuka Baba, Yasuhiro Endo, Hiroaki Toyama, Yutaka Ejima, Mitsunobu Matsubara, Masahiro Tachi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Background/Aims: Salicylate causes drug-induced immune thrombocytopenia. However, some clinical studies indicate the presence of additional mechanisms in the drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. Since salicylate is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate on the membrane capacitance in rat megakaryocytes. Taking electron microscopic imaging of the cellular surface, we also examined the effects of salicylate on the membrane micro-architecture of megakaryocytes. Results: Salicylate significantly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging technique. As shown by electron microscopy, salicylate actually halted the process of pro-platelet formation in megakaryocytes. Conclusion: This study demonstrated for the first time that salicylate inhibits the process of thrombopoiesis in megakaryocytes, as detected by the decrease in the membrane capacitance. Salicylate-induced changes in the membrane micro-architecture are thought to be responsible for its effects.

Original languageEnglish
Pages (from-to)2371-2382
Number of pages12
JournalCellular Physiology and Biochemistry
Volume35
Issue number6
DOIs
Publication statusPublished - 2015 Jun 19

Keywords

  • Megakaryocytes
  • Membrane capacitance
  • Membrane micro-architecture
  • Salicylate
  • Thrombopoiesis

ASJC Scopus subject areas

  • Physiology

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