Identification of Heme Oxygenase 1 (HO-1) as a Novel Negative Regulator of Mobilization of Hematopoietic Stem/Progenitor Cells

Marcin Wysoczynski, Janina Ratajczak, Daniel Pedziwiatr, Gregg Rokosh, Roberto Bolli, Mariusz Z. Ratajczak

Research output: Contribution to journalArticlepeer-review

Abstract

Activation of complement cascade (ComC) play and important role in mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB). While there are vast experimental data on the mechanisms and factors that induce or promote mobilization of HSPCs, there is relatively less data on negative regulators of this process. We demonstrate for the first time that heme oxygenase-1 (HO-1) that has a well-documented anti-inflammatory potential plays an important and heretofore unrecognized role in retention of HSPCs in BM niches by i) modulating negatively activation of mobilization promoting ComC, ii) maintaining stromal derived factor-1 (SDF-1) level in the BM microenvironment and iii) attenuating chemotactic responsiveness of HSPCs to SDF-1 and sphingosine-1 phosphate (S1P) gradients in PB. Furthermore, our data showing a positive mobilizing effect by a non-toxic small-molecule inhibitor of HO-1 (SnPP) suggest that blockade of HO-1 would be a promising strategy to facilitate mobilization of HSPCs. Further studies are also needed to evaluate better the molecular mechanisms responsible for the potential effect of HO-1 in homing of HSPCs after transplantation.

Original languageEnglish (US)
Pages (from-to)110-118
Number of pages9
JournalStem Cell Reviews and Reports
Volume11
Issue number1
DOIs
StatePublished - Feb 2015

Keywords

  • Complement Cascade
  • Heme oksygenase-1
  • SDF-1
  • Stem cell mobilization

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

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