SDF-1alpha-induced intracellular calcium transient involves Rho GTPase signalling and is required for migration of hematopoietic progenitor cells.
Signalling through the chemokine stromal derived factor (SDF)-1alpha and its receptor CXCR4 has been recognized as a key event in the migratory response of hematopoietic stem and progenitor cells (HPC). Small GTPases of the Rho/Rac family might be involved in SDF-1alpha signalling at several different levels. In the present study we report that two toxins from Clostridium species which inhibit the small GTPase Rho suppressed SDF-1alpha-induced generation of intracellular calcium transients in HPC. Chelation of intracellular Ca(2+) with BAPTA or depletion of intracellular Ca(2+) stores with thapsigargin demonstrated that calcium transients are essential for SDF-1alpha-induced chemotactic migration of HPC. Furthermore, transplantation of HPC pretreated with Ca(2+) flux inhibitors into mice revealed a suppression of HPC homing to the bone marrow and increased levels of cells remaining in the bloodstream or circulating to the spleen. Our data indicate that the small GTPase Rho is required for the induction of Ca(2+) transients in HPC, which in turn are necessary for the coordinated migratory response of HPC both in vitro and in vivo.
Henschler
Reinhard
R
Department of Production, DRK Institute of Transfusion Medicine and Immune Hematology, Germany. rhenschler@web.de
Piiper
Albrecht
A
Bistrian
Roxana
R
Möbest
Dietrich
D
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D039902:Multipotent Stem Cells / Q000187:drug effects / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D004533:Egtazic Acid; D019284:Thapsigargin; D020741:rho GTP-Binding Proteins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid