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Murine lineage marker (Lin) ~-Sca-l~+ c-kit~+ and Lin ~-Sca-l~- c-kit~+ cells represent the primitive hematopoietic stem cells (HSC)and coommitted hematopoietic progenitor cells(HPC),respectively. The number of Lin ~-Sca-l~+ c-kit ~+HSCs in bone marrow was significantly increased (2.9folds) in tumor necrosis factor(TNF)-receptor-55(TNF-R55)-deficient mice compared with that of wildtype ones without marked change in cellularity of bone marrow. Both in the methylcellulose culture and a single cell proliferation assay,mouse TNFα(mTNFα)inhibited in vitro the proliferation of wild type mouse-derived Lin-Sca-l~+ c-kit~+ cells stimulated with the combination of multiple growth factors as well as that of Lin ~-Sca-l~- c-kit~+ cells stimulated with granulocyte-colony stimulating factor (G-CSF) plus stem cell factor (SCF).Human TNFα(hTNFα),which selectively binds to mouse TNF-R55 but not to mouse TNF-R75, exhibited similar spectrum of inhibitory effects as mTNFα
Murine lineage marker (Lin) ~ -Sca-1 ~ + c-kit ~ + and Lin ~ -Sca-1 ~ -c-kit ~ + cells represent the primitive hematopoietic stem cells (HSC) and coommitted hematopoietic progenitor cells (HPC) , respectively. The number of Lin ~ -Sca-1 ~ + c-kit ~ + HSCs in bone marrow was significantly increased (2.9folds) in tumor necrosis factor (TNF) -receptor-55 with that of wildtype ones without marked change in cellularity of bone marrow. Both in the methylcellulose culture and a single cell proliferation assay, mouse TNFα (mTNFα) inhibited in vitro the proliferation of wild type mouse-derived Lin-Sca-1 ~ + c -kit ~ + cells stimulated with the combination of multiple growth factors as well as that of Lin ~ -Sca-1 ~ -c-kit ~ + cells stimulated with granulocyte-colony stimulating factor (G-CSF) plus stem cell factor ). Human TNFα (hTNFα), which selectively binds to mouse TNF-R55 but not to mouse TNF-R75, showed similar spectrum of inhibitory effects as mTNFα