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

✍ Scribed by Elisabetta Melloni; Paola Secchiero; Claudio Celeghini; Diana Campioni; Vittorio Grill; Lia Guidotti; Giorgio Zauli

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 391 KB
• Volume: 204
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20358

✦ Synopsis

Abstract

The expression and function of surface TRAIL and TRAIL receptors were investigated in primary megakaryocytic cells, generated in serum‐free 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^+^/CD41^dim^ 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. © 2005 Wiley‐Liss, Inc.