Leukemia inhibitory factor differentiation-inhibiting activity/human interleukin for DA cells augments proliferation of human hematopoietic stem cells.
Leukemia inhibitory factor (LIF)/differentiation-inhibiting activity (DIA)/human interleukin for DA cells (HILDA) is a cytokine with biologic activities involving a variety of different types of target cells. Here we have tested LIF/DIA for possible effects on the growth and differentiation of normal human hematopoietic cells in culture. As a single agent, LIF/DIA had no effect on colony formation by CD34-positive human bone marrow cells. However, LIF/DIA was as effective as either interleukin-6 (IL-6) or granulocyte colony-stimulating factor (G-CSF) in the enhancement of IL-3-dependent colony formation of very primitive blast colony-forming cells. Studies using neutralizing antibodies against IL-6 or G-CSF demonstrated that this was not due to induction in culture of either of the other known synergistic factors for blast cell colony formation. A 1-day delay in the time course of appearance of blast cell colonies grown in the presence of LIF/DIA relative to those grown in the presence of IL-6 suggests that the different synergistic factors may operate through different mechanisms, although we cannot rule out that high doses of LIF/DIA might yield accelerated blast cell colony formation. Our findings provide evidence that LIF/DIA may play an important role, along with IL-6 and G-CSF, in the regulation of early hematopoietic stem cells.
VA Medical Center, Charleston, SC 29403.
A G
AG
Leary
G G
GG
Wong
S C
SC
Clark
A G
AG
Smith
M
M
Ogawa
D000906:Antibodies / Q000276:immunology; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor; D006131:Growth Inhibitors / Q000494:pharmacology*; D006397:Hematinics / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*
D000906:Antibodies; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D006397:Hematinics; D007377:Interleukin-3; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D016179:Granulocyte Colony-Stimulating Factor