Retinoic acid modulates IL-5 receptor expression and selectively inhibits eosinophil-basophil differentiation of hemopoietic progenitor cells.
BACKGROUND
IL-5 plays a central role in eosinophil and basophil differentiation, exerting its effects through the IL-5 receptor (IL-5Ralpha). Currently, little is known concerning regulation of IL-5Ralpha expression in the context of commitment of hemopoietic progenitor cells to the eosinophil and basophil lineages.


OBJECTIVE
Because all-trans retinoic acid (ATRA) is known to modulate some aspects of hemopoietic differentiation, we examined the effects of ATRA on eosinophil-basophil differentiation and IL-5Ralpha expression.


METHODS
Progenitor cells were obtained from bone marrow aspirates and cord blood samples. Enriched populations of CD34(+) cells were isolated by means of positive immunomagnetic selection with MACS beads.


RESULTS
In semisolid methylcellulose cultures of normal human bone marrow, ATRA (10(-6) mol/L) selectively suppressed eosinophil-basophil colony-forming units but had no effect on granulocyte-macrophage colony-forming units. Similarly, ATRA (10(-6) mol/L) inhibited eosinophil-basophil differentiation of cord blood CD34(+) cells in liquid culture, whereas neutrophil differentiation proceeded without impediment. Most importantly, these effects of ATRA (10(-8) to 10(-6) mol/L) on CD34(+) cells were associated with a dose-dependent inhibition of IL-5Ralpha but no change in GM-CSF receptor expression, as detected with flow cytometry.


CONCLUSIONS
These findings indicate that retinoids can differentially regulate expression of IL-5Ralpha, but not GM-CSF receptor, and that these effects have functional consequences in vitro on eosinophil and basophil differentiation.
Upham
John W
JW
Department of Medicine, University of Western Australia, Perth, Australia.
Sehmi
Roma
R
Hayes
Lisa M
LM
Howie
Karen
K
Lundahl
Joachim
J
Denburg
Judah A
JA
D018952:Antigens, CD34 / Q000378:metabolism; D001491:Basophils / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004804:Eosinophils / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018123:Receptors, Interleukin / Q000378:metabolism*; D053649:Receptors, Interleukin-5; D014212:Tretinoin / Q000494:pharmacology*
D018952:Antigens, CD34; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D014212:Tretinoin