title: Identification of heme oxygenase 1 (HO-1) as a novel negative regulator of mobilization of hematopoietic stem/progenitor cells.
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.
authors.affiliation: Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wysoczynski
authors.forename: Janina
authors.initials: J
authors.lastname: Ratajczak
authors.forename: Daniel
authors.initials: D
authors.lastname: Pedziwiatr
authors.forename: Gregg
authors.initials: G
authors.lastname: Rokosh
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D003114:Colony-Forming Units Assay; D050776:Complement C5b / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007958:Leukocyte Count; D008246:Lysophospholipids / Q000378:metabolism; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D011524:Protoporphyrins / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D003186:Complement C9; C515256:Cxcl12 protein, mouse; D008246:Lysophospholipids; D011524:Protoporphyrins; D016179:Granulocyte Colony-Stimulating Factor; C060506:sphingosine 1-phosphate; D050776:Complement C5b; C028025:protoporphyrin IX; D051547:Heme Oxygenase-1; D013110:Sphingosine
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