Cytotoxic lymphocyte maturation factor (interleukin 12) is a synergistic growth factor for hematopoietic stem cells.
The recently cloned cytotoxic lymphocyte maturation factor (interleukin 12 [IL-12]) has been described as a growth factor for mature lymphocytes. The present study investigated whether purified recombinant murine IL-12 (rMuIL-12) also could affect the proliferation of primitive bone marrow progenitor cells. Using a population of Lin-Sca-1+ murine bone marrow stem cells, we now demonstrate that IL-12 is a potent synergistic factor for primitive hematopoietic stem cells. The synergy of IL-12 was observed in single-cell cloning assays, demonstrating that its effects are directly mediated. Specifically, IL-12 enhanced stem cell factor-induced myelopoiesis of Lin-Sca-1+ cells sevenfold, and synergized with colony-stimulating factors (CSFs) to induce proliferation of Lin-Sca-1+ stem cells. IL-12 increased the number of responding progenitor cells as well as the size of the colonies formed. IL-12 also increased colony formation of high proliferative potential colony-forming cells with multiple CSF combinations. The effects of IL-12 were concentration dependent with a 50% effective dose of 2-20 and 20-200 ng/ml, resulting in maximum stimulation. Furthermore, a neutralizing anti-IL-12 antibody blocked the synergistic effects of rMuIL-12. In addition, IL-12 was found to have synergistic effects on more committed bone marrow progenitors as well. Our results therefore suggest that in addition to being a potent lymphopoietic stimulator, IL-12 is a regulator of the growth of hematopoietic stem cells and their myeloid progeny.
Jacobsen
S E
SE
Department of Immunology, Norwegian Radium Hospital, Oslo.
Veiby
O P
OP
Smeland
E B
EB
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D019089:Stem Cell Factor
D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D007378:Interleukins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor