title: The Involvment of Hematopoietic-Specific PLC -β2 in Homing and Engraftment of Hematopoietic Stem/Progenitor Cells.
abstract: Migration and bone marrow (BM) homing of hematopoietic stem progenitor cells (HSPCs) is regulated by several signaling pathways, and here we provide evidence for the involvement in this process of hematopoietic-specific phospholipase C-β2 (PLC-β2). This enzyme is involved in release of intracellular calcium and activation of protein kinase C (PKC). Recently we reported that PLC-β2 promotes mobilization of HSPCs from BM into peripheral blood (PB), and this effect is mediated by the involvement of PLC-β2 in the release of proteolytic enzymes from granulocytes and its role in disintegration of membrane lipid rafts. Here we report that, besides the role of PLC-β2 in the release of HSPCs from BM niches, PLC-β2 regulates the migration of HSPCs in response to chemotactic gradients of BM homing factors, including SDF-1, S1P, C1P, and ATP. Specifically, HSPCs from PLC-β2-KO mice show impaired homing and engraftment in vivo after transplantation into lethally irradiated mice. This decrease in migration of HSPCs can be explained by impaired calcium release in PLC-β2-KO mice and a high baseline level of heme oxygenase 1 (HO-1), an enzyme that negatively regulates cell migration.
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Adamiak
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA.
authors.forename: Malwina
authors.initials: M
authors.lastname: Suszynska
authors.affiliation: Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel-Latif
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdelbaset-Ismail
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA.
authors.forename: Janina
authors.initials: J
authors.lastname: Ratajczak
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA. mzrata01@louisville.edu.|Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland. mzrata01@louisville.edu.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology; D054377:Chemokine CXCL12 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000201:enzymology; D008246:Lysophospholipids / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002518:Ceramides; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D005353:Fibronectins; D008246:Lysophospholipids; C065576:ceramide 1-phosphate; C060506:sphingosine 1-phosphate; D000255:Adenosine Triphosphate; D051547:Heme Oxygenase-1; D054799:Phospholipase C beta; D013110:Sphingosine; D002118:Calcium
keywords: C1P; HO-1; PLC-β2; S1P; SDF-1; Stem cell homing