Functional expression of TRAIL and TRAIL-R2 during human megakaryocytic development

Elisabetta Melloni, Paola Secchiero, Claudio Celeghini, Diana Campioni, Vittorio Grill, Lia Guidotti, Giorgio Zauli

Research output: Contribution to journalArticle

Abstract

The expression and function of surface TRAIL and TRAIL receptors were investigated in primary megakaryocytic cells, generated in serum-tree liquid phase from peripheral human CD34+ cells. The surface expression of both TRAIL and "death receptor" TRAIL-R2 became detectable starting from the early phase of megakaryocytic differentiation (day 6 of culture) and persisted at later (days10-14) culture times. On the other hand, "death receptor" TRAIL-R1, "decoy receptors" TRAIL-R3, and TRAIL-R4 were barely detectable or undetectable at any time point examined. Addition of recombinant TRAIL at day 6 of culture increased the rate of spontaneous apoptosis of CD34+/CD41dim megakaryoblasts and it significantly decreased the total output of mature megakaryocytic cells evaluated after additional 4-8 days of culture. Conversely, addition in culture of TRAIL-R2-Fc chimera, which blocked the interaction between endogenous TRAIL and TRAIL-R2 on the surface of cultured megakaryocytic cells, increased the total megakaryocytic cell count. In addition, recombinant TRAIL promoted a small but reproducible increase of maturation in the surviving megakaryocytic cell population, evaluated by both phenotypic analysis and morphology. A similar pro-maturation effect was observed when TRAIL was added to bone marrow-derived CD61+ megakaryocytic cells. Thus, our data suggest a role of TRAIL as a regulator of megakaryocytopoiesis.

Original languageEnglish
Pages (from-to)975-982
Number of pages8
JournalJournal of Cellular Physiology
Volume204
Issue number3
DOIs
Publication statusPublished - Sep 2005

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ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Melloni, E., Secchiero, P., Celeghini, C., Campioni, D., Grill, V., Guidotti, L., & Zauli, G. (2005). Functional expression of TRAIL and TRAIL-R2 during human megakaryocytic development. Journal of Cellular Physiology, 204(3), 975-982. https://doi.org/10.1002/jcp.20358