P-selectin, and not E-selectin, negatively regulates murine megakaryocytopoiesis.
To assess the role of P-selectin and E-selectin in megakaryocytopoiesis, in vitro assays were performed in animal models deficient in both adhesion receptors. There was a significantly greater number of IL-3-responsive megakaryocyte progenitors CFU (CFU-MK) and an increase in immature megakaryoblasts in response to IL-6 in the P-selectin-null mice compared with the wild-type controls. Furthermore, P-selectin-null mice showed a greater number of CFU-MK colonies derived from CD34(+) cells in response to IL-3 or IL-3 plus stem cell factor. A significant shift in baseline ploidy with a reduction in 8N cells and an increase in 32N cells was also observed in the P-selectin-null mice. Secretion of the inhibitory growth factor TGF-beta1 and not TGF-beta2 was significantly lower in the supernatants of cultures containing bone marrow cells from P-selectin-deficient mice as compared with those from the wild-type control bone marrow cells. No differences in the responsiveness of murine CFU-MK, immature megakaryocytes, or 5-fluorouracil-selected stem cells to cytokines were observed in E-selectin-null mice as compared with the control mice. These studies indicate that the absence of P-selectin, and not E-selectin, resulted in an altered adhesion environment with subsequent expansion of megakaryocyte progenitors and immature megakaryoblasts, enhanced secretion of TGF-beta1, and apparent increased responsiveness to inflammatory cytokines.
Banu
Naheed
N
Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA.
Avraham
Shalom
S
Avraham
Hava Karsenty
HK
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D019040:E-Selectin / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D034061:Thrombopoiesis / Q000235:genetics / Q000276:immunology*; D013926:Thrombopoietin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D019040:E-Selectin; D007106:Immune Sera; D015850:Interleukin-6; D019007:P-Selectin; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013926:Thrombopoietin