Effects of glucocorticoids and mineralocorticoids on proliferation and maturation of human peripheral blood stem cells.
It has been shown that hematopoietic progenitors can be expanded ex vivo in the presence of various cytokine combinations. Glucocorticoids (GC) are involved in the self-renewal of erythroid progenitors in chicken. To see whether GC have a similar effect on hematopoiesis in humans, CD34(+) peripheral blood stem cells were cultured in serum free medium in the presence of a GC, triamcinolone acetonide. However, our results demonstrate an inhibition of both erythroid and granulocyte-macrophage (GM) proliferation and a modification of erythroid colony morphology. Furthermore, RU38486 (Mifepristone), a potent GC antagonist, was unable to reverse the inhibitory effect of triamcinolone acetonide. We also identified and characterized another steroid subfamily, the mineralocorticoid (MC) subfamily, in human PB CD34(+) cells. The MC, aldosterone, significantly enhanced GM colony formation and diminished the erythroid colony number. Neither of effects were inhibited by ZK91587, an antagonist specific to the MC receptor (MCR). In contrast, ZK91587 reversed the stimulatory effect of deoxycorticosterone on GM colony formation. Cytoplasmic staining for MCR was observed in CD34(+) cells incubated with a polyclonal antiserum raised against human MCR. To our knowledge, this is the first demonstration of the presence of MCR in human PB CD34(+) cells.
Grafte-Faure
S
S
Research Department of Microenvironment, (MERCI), Rouen Cedex, France.
Leveque
C
C
Vasse
M
M
Soria
C
C
Norris
V
V
Vannier
J P
JP
D000328:Adult; D000450:Aldosterone / Q000494:pharmacology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D005938:Glucocorticoids; D007377:Interleukin-3; D008901:Mineralocorticoids; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D013148:Spironolactone; D015735:Mifepristone; D003900:Desoxycorticosterone; D000450:Aldosterone; C054537:ZK 91587; D014222:Triamcinolone Acetonide