title: Fas ligand promotes cell survival of immature human bone marrow CD34+CD38- hematopoietic progenitor cells by suppressing apoptosis.
abstract: Fas (CD95, APO-1) is a member of the TNF receptor family, and engagement of Fas by its ligand, Fas ligand (FasL), can induce apoptotic death of Fas expressing cells. Signaling through Fas has previously been shown to induce apoptosis of CD34+ human hematopoietic progenitor cells after exposure to IFN-gamma or TFN-alpha. In contrast, we found that FasL promoted a significantly increased viability of primitive CD34+CD38- cells. Thus, incubation with FasL for 48 hours reduced cell death from 46 to 29% compared to cells cultured in medium alone as measured by propidium iodide (PI) incorporation (n = 8, p < 0.02). Inhibition of apoptosis was confirmed by morphological analysis and by the Nicoletti technique. Furthermore, by using a delayed addition assay at the single cell level we found that sFasL treatment had a direct viability-promoting effect on CD34(+)CD38(-) cells. The effect of sFasL was completely blocked by NOK-1, a neutralizing mAb against FasL. In agreement with previous reports, FasL alone slightly increased cell death of more mature CD34(-)CD38+ cells, indicating an interesting shift in the responsiveness to FasL during early hematopoiesis.
authors.affiliation: Department of Immunology, The Norwegian Radium Hospital, Oslo, Norway. dag.josefsen@labmed.uio.no
authors.forename: D
authors.initials: D
authors.lastname: Josefsen
authors.forename: J H
authors.initials: JH
authors.lastname: Myklebust
authors.forename: D H
authors.initials: DH
authors.lastname: Lynch
authors.forename: T
authors.initials: T
authors.lastname: Stokke
authors.forename: H K
authors.initials: HK
authors.lastname: Blomhoff
authors.forename: E B
authors.initials: EB
authors.lastname: Smeland
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002470:Cell Survival; D053222:Fas Ligand Protein; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D009244:NAD+ Nucleosidase / Q000032:analysis; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019014:fas Receptor / Q000502:physiology
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016298:Hematopoietic Cell Growth Factors; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1