Premium
Stroma‐derived factor 1α induces a selective inhibition of human erythroid development via the functional upregulation of Fas/CD95 ligand
Author(s) -
Gibellini Davide,
Bassini Alessandra,
Re Maria Carla,
Ponti Cristina,
Miscia Sebastiano,
Gonelli Arianna,
La Placa Michele,
Zauli Giorgio
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2000.02386.x
Subject(s) - stem cell factor , haematopoiesis , biology , erythropoiesis , microbiology and biotechnology , cxc chemokine receptors , downregulation and upregulation , glycophorin , erythropoietin , progenitor cell , decay accelerating factor , granulocyte macrophage colony stimulating factor receptor , receptor , antigen , immunology , stem cell , chemokine , chemokine receptor , macrophage , in vitro , endocrinology , macrophage colony stimulating factor , medicine , biochemistry , complement system , antibody , anemia , gene
CXC chemokine receptor 4 (CXCR4), the high‐affinity receptor for stroma‐derived factor 1α (SDF‐1α), shows distinct patterns of expression in human CD34 + haematopoietic progenitor cells induced to differentiate in vitro along the granulocytic and erythroid lineages. In serum‐free liquid cultures supplemented with stem cell factor (SCF), interleukin 3 (IL‐3) and granulocyte colony‐stimulating factor, the expression of surface CXCR4 progressively increased in cells differentiating along the granulocytic lineage. The addition in culture of 200 ng/ml of SDF‐1α, a concentration which maximally activated intracellular Ca 2+ flux, only modestly affected the expression levels of CD15 and CD11b granulocytic antigens, as well as the total number of viable cells. On the other hand, in liquid cultures supplemented with SCF, IL‐3 and erythropoietin, SDF‐1α induced the downregulation of glycophorin A erythroid antigen, accompanied by a progressive decline in the number of viable erythroblasts. Moreover, in semisolid assays, SDF‐1α significantly reduced the number of plurifocal erythroid colonies (erythroid blast‐forming units; BFU‐E), whereas it did not affect granulocyte–macrophage colony‐forming units (CFU‐GM). We also demonstrated that the inhibitory effect of SDF‐1α on glycophorin A + erythroid cell development was mediated by the functional upregulation of CD95L in erythroid cultures. These data indicate that SDF‐1α plays a role as a negative regulator of erythropoiesis.