PMID- 8704242 OWN - NLM STAT- MEDLINE DCOM- 19960912 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 88 IP - 3 DP - 1996 Aug 1 TI - Direct synergistic effects of leukemia inhibitory factor on hematopoietic progenitor cell growth: comparison with other hematopoietins that use the gp130 receptor subunit. PG - 863-9 AB - Because leukemia inhibitory factor (LIF) has little or no effect on murine hematopoietic progenitor cell growth yet enhances hematopoiesis in vivo, we sought to determine whether the effects of LIF were directly or indirectly mediated, or a combination of both. Although LIF alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) has no effect on colony formation of unfractionated bone marrow cells (BMCs), it enhances M-CSF-induced colony formation. In comparison, LIF synergizes with IL-3, GM-CSF, M-CSF, and Steel Factor (SLF) to promote the colony formation of partially purified lineage-negative (Lin-) BM progenitors without altering their differentiation. These effects were directly mediated since identical results were observed in single-cell assays. Comparing the effect of LIF with other members of this subclass of hematopoietins (IL-6, oncostatin M [OSM], and ciliary neurotrophic factor [CNTF]), we found that while LIF and IL-6 equally synergize with M-CSF and SLF to promote the colony formation of Lin- BMCs, OSM, and CNTF have no effect. In agreement with OSMs ability to directly bind gp130, preincubation of BMCs with OSM inhibits progenitor cell growth stimulated by the combination of LIF or IL-6 plus SLF. LIF can also directly enhance the growth of further purified more primitive Lin- c-kit+ progenitor cells in the presence of IL-3, GM-CSF, or SLF. Thus, LIF can directly synergize with growth factors to promote the proliferation of purified hematopoietic progenitors, suggesting that the direct effects of LIF on hematopoietic cell growth can, in part, explain the observed hematopoietic effects in vivo. This is a US government work. There are no restrictions on its use. FAU - Keller, J R AU - Keller JR AD - Biological Carcinogenesis and Development Program, Science Applications International Corporation Frederick, MD, USA. FAU - Gooya, J M AU - Gooya JM FAU - Ruscetti, F W AU - Ruscetti FW LA - eng GR - N01-CO-56000/CO/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Growth Inhibitors) RN - 0 (Hematopoietic Cell Growth Factors) RN - 0 (IL6ST protein, human) RN - 0 (Il6st protein, mouse) RN - 0 (Interleukin-3) RN - 0 (Interleukin-6) RN - 0 (LIF protein, human) RN - 0 (Leukemia Inhibitory Factor) RN - 0 (Lif protein, mouse) RN - 0 (Lymphokines) RN - 0 (Membrane Glycoproteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (OSM protein, human) RN - 0 (Osm protein, mouse) RN - 0 (Peptides) RN - 0 (Recombinant Proteins) RN - 0 (Stem Cell Factor) RN - 106956-32-5 (Oncostatin M) RN - 133483-10-0 (Cytokine Receptor gp130) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) SB - IM MH - Animals MH - Antigens, CD/*drug effects/physiology MH - Bone Marrow Cells MH - Cell Division/drug effects MH - Ciliary Neurotrophic Factor MH - Colony-Forming Units Assay MH - Cytokine Receptor gp130 MH - Drug Synergism MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Growth Inhibitors/*pharmacology MH - Hematopoietic Cell Growth Factors/*pharmacology MH - Hematopoietic Stem Cells/*drug effects MH - Humans MH - Interleukin-3/pharmacology MH - *Interleukin-6 MH - Leukemia Inhibitory Factor MH - Lymphokines/*pharmacology MH - Macrophage Colony-Stimulating Factor/pharmacology MH - Membrane Glycoproteins/*drug effects/physiology MH - Mice MH - Mice, Inbred BALB C MH - Nerve Tissue Proteins/pharmacology MH - Oncostatin M MH - Peptides/pharmacology MH - Proto-Oncogene Proteins c-kit/analysis MH - Recombinant Proteins/pharmacology MH - Stem Cell Factor/pharmacology EDAT- 1996/08/01 00:00 MHDA- 1996/08/01 00:01 CRDT- 1996/08/01 00:00 PHST- 1996/08/01 00:00 [pubmed] PHST- 1996/08/01 00:01 [medline] PHST- 1996/08/01 00:00 [entrez] AID - S0006-4971(20)62509-5 [pii] PST - ppublish SO - Blood. 1996 Aug 1;88(3):863-9.