Recruitment of primitive peripheral blood cells: synergism of interleukin 12 with interleukin 6 and stem cell factor.
Interleukin-12 (IL-12), a heterodimeric cytokine with potent biological activity, was evaluated for effects on proliferation of human immature progenitor cells in vitro. In vitro proliferation of 5-FU-resistant CD34+ (G0) peripheral blood stem cells (PBSC) in response to sequential cytokine stimulation was examined in the presence and absence of 100 ng/ml IL-12. PBSC were found to include a subpopulation of cells that were resistant to 25 microg/ml 5-FU and required a combination of IL-12, IL-6 and SCF for the production of morphologically recognizable clonogenic elements at day 14 in semisolid medium. Furthermore, addition of IL-6 soluble receptor (IL-6Rs) to IL-6 and SCF led to a similar recruitment. We also demonstrated a significant production of IL-6Rs by CD34+ cells stimulated by IL-12. We noted that glucocorticoids and aldosterone, a mineralocorticoid, had a positive effect on recruitment, but neither mineralocorticoid nor glucocorticoids induced IL-6Rs production by CD34+ cells. The recruitment mechanism by steroids seemed to be different from that used by IL-12. These results confirm previous findings which showed the involvement of IL-12 on immature PBSCs and suggest that IL-12 might play a key role in early haemopoiesis.
Grafte-Faure
S
S
Research Department of Microenvironment and Cell Integrated Renewal (MERCI), Rouen, and IFR Physiocochemistry and Biology of Integrated Systems (CNRS 61), France.
Leveque
C
C
Vasse
M
M
Soria
C
C
Vannier
J P
JP
D018952:Antigens, CD34; D002454:Cell Differentiation / Q000502:physiology; D016895:Culture Media, Serum-Free; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D019089:Stem Cell Factor
D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D019089:Stem Cell Factor; D018664:Interleukin-12; D005472:Fluorouracil