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 C XC-chemokine receptor 4 (CXCR4), was added to human CD34(+) hematopoietic p rogenitor 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 (I L-3), macrophage-colony stimulating factor (M-CSF), and 10% fetal calf seru m (FCS), or, SCF and thrombopoietin (TPO), the expression of surface CXCR4 progressively increased in both the CD14(+) monocytic and CD41(+) megakaryo cytic lineages. While SDF-1 alpha caused only modest effects on cells of th e monocytic lineage, it induced profound down-regulation of CXCR4 in megaka ryocytic cells at all stages of differentiation. Moreover, while SDF-1 alph a initially up-regulated the early megakaryocytic antigen CD41, at later ti me points (days 12-16) it induced down-regulation of the late megakaryocyti c antigen CD42b. Consistently, at day 16, the number of mature megakaryocyt es was significantly decreased in cultures supplemented with SDF-1 alpha. T hese findings indicate that, besides its primary role in regulating the ret ention of precursor cells in hematopoietic tissues, the SDF-1 alpha/CXCR4 s ystem participates in the regulation of megakaryocytic development by stimu lating the formation of immature megakaryoblasts and inhibiting the formati on of mature megakaryocytes. Anat Rec 260. 141-147, 2000. (C) 2000 Wiley-Li ss, Inc.