Fetal Liver Hematopoiesis Becomes Sensitive to Estrogen after Transplantation to Adult Mice

Konference: 2006 48th ASH Annual Meeting - účast ČR

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Publikace ve sborníku

Číslo abstraktu: 4164

Autoři: Ko-Tung Chang; Tereza Pelichovska; RNDr. Luděk Šefc, CSc.; Petr Broulik; Prof. MUDr. Emanuel Nečas, DrSc.

The hematopoietic stem/progenitor cells from fetal liver (FL) of the mouse do not express estrogen receptors in contrast to the cells from adult bone marrow (BM) [Igarashi H et al: Proc Natl Acad Sci USA (2001) 98, 15131-15136]. Since estrogen had been shown to suppress B-lymphopoiesis in vivo [Medina KL et al: Blood (2000) 95, 2059-2067; Erlandsson MC: Immunology (2003) 108, 346-351], we investigated estrogen action on B-lymphopoiesis derived from FL cells transplanted to adult mice. FL cells from E14.5 embryos of C57Bl/6 mice (Ly5.1), or a mixture of FL cells (Ly5.1) with BM cells (Ly5.2), were transplanted either into sublethally (7 Gy) or into lethally (11 Gy) irradiated male Ly5.2 recipients, respectively. Half of the recipients were kept on a diet containing estradiol (estimated intake of 100 micrograms/day). Peripheral blood obtained from the retrobulbar venous plexus was analyzed for presence of Ly5.1 (FL origin) or Ly5.2 (BM origin) WBCs using flow cytometry (FACS Calibur, Becton Dickinson) from 2 weeks up to 16 weeks after transplantation. The WBCs were also stained with anti-mouse CD45R/B220 antibody to detect B-lymphocytes. Numbers of repopulating B-lymphocytes of FL origin were little affected by estrogen 2 and 4 weeks after transplantation while those of BM origin were significantly suppressed. However, the difference between responses of FL or BM origin B-lymphopoiesis to estrogen became much smaller after 8 weeks and was not evident after 16 weeks. The chimeric bone marrow was further transplanted to secondary lethally irradiated recipients and effect of estrogen on B-lymphopoiesis of either FL or BM origin was studied for another 20 weeks. In this case B-lymphopoiesis of FL origin was suppressed by estrogen immediately after transplantation similarly as that of BM origin. The results provide a functional confirmation of previously reported molecular differences between FL and adult BM stem/progenitor cells dwelling in lack of the expression of estrogen receptors in the FL cells. They also conclusively demonstrate that FL stem/progenitor cells become invariably sensitive to estrogen after being exposed to the environment of the adult organism for a long enough time.

Datum přednesení příspěvku: 9. 12. 2006