Differential effects of stromal derived factor-1 alpha (SDF-1 alpha) on early and late stages of human megakaryocytic development.
Stromal derived factor-1 alpha (SDF-1 alpha), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), was added to human CD34(+) hematopoietic progenitor cells that can be induced to differentiate along the monocytic or megakaryocytic lineages. In control liquid cell cultures supplemented with two different cytokine cocktails: stem cell factor (SCF), interleukin-3 (IL-3), macrophage-colony stimulating factor (M-CSF), and 10% fetal calf serum (FCS), or, SCF and thrombopoietin (TPO), the expression of surface CXCR4 progressively increased in both the CD14(+) monocytic and CD41(+) megakaryocytic lineages. While SDF-1 alpha caused only modest effects on cells of the monocytic lineage, it induced profound down-regulation of CXCR4 in megakaryocytic cells at all stages of differentiation. Moreover, while SDF-1 alpha initially up-regulated the early megakaryocytic antigen CD41, at later time points (days 12-16) it induced down-regulation of the late megakaryocytic antigen CD42b. Consistently, at day 16, the number of mature megakaryocytes was significantly decreased in cultures supplemented with SDF-1 alpha. These findings indicate that, besides its primary role in regulating the retention of precursor cells in hematopoietic tissues, the SDF-1 alpha/CXCR4 system participates in the regulation of megakaryocytic development by stimulating the formation of immature megakaryoblasts and inhibiting the formation of mature megakaryocytes.
Secchiero
P
P
Department of Morphology and Embryology, Human Anatomy Section, University of Ferrara, 44100 Ferrara, Italy.
Celeghini
C
C
Cutroneo
G
G
Di Baldassarre
A
A
Rana
R
R
Zauli
G
G
D018952:Antigens, CD34 / Q000032:analysis / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008533:Megakaryocytes / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis / Q000096:biosynthesis; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000032:analysis / Q000096:biosynthesis
D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D019718:Receptors, CXCR4