Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro

Blood. 1995 Oct 15;86(8):2930-7.

Abstract

Murine bone marrow cells with lineage phenotypes (Lin)-Sca-1+c-kit+ and Lin-Sca-1-c-kit+ cells represent primitive hematopoietic stem cells (HSCs) and committed hematopoietic progenitor cells, respectively. The number of Lin-Sca-1+c-kit+ HSCs in bone marrow was significantly increased in tumor necrosis factor (TNF) receptor p55-deficient (TNF-R55-1-) mice compared with the TNF-R55+/+ wild-type mice without a marked change in bone marrow cellularity. In both the methylcellulose culture and a single-cell proliferation assay, mouse TNF alpha (mTNF alpha) inhibited in vitro the proliferation of wild-type mouse-derived Lin-Sca-1+c-kit+ cells in response to a combination of multiple growth factors. The same is true for that of Lin-Sca-1+c-kit+ cells stimulated with granulocyte colony-stimulating factor (G-CSF) plus stem cell factor (SCF). Moreover, mTNF alpha significantly arrested the entry into S-phase from G0/G1 phase of Lin-Sca-1+c-kit+ cells stimulated with multiple growth factors and Lin-Sca-1-c-kit+ cells stimulated with G-CSF plus SCF. In contrast, mTNF alpha failed to affect the growth and cell cycle progression of Lin-Sca-1+c-kit+ cells and Lin-Sca-1-c-kit+ cells that were obtained from TNF-R55-deficient mice. These data suggest that TNF may be an important physiologic regulator of hematopoiesis and that TNF-R55 may be essentially involved in TNF-mediated inhibition of the growth of both primitive stem and more committed progenitor cells.

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Ly
  • Cell Division / drug effects
  • Cell Lineage
  • Cells, Cultured
  • Female
  • Growth Inhibitors / pharmacology*
  • Hematopoietic Cell Growth Factors / pharmacology*
  • Hematopoietic Stem Cells / cytology*
  • Interleukin-6 / pharmacology
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-kit
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins / pharmacology
  • Specific Pathogen-Free Organisms
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Antigens, CD
  • Antigens, Ly
  • Growth Inhibitors
  • Hematopoietic Cell Growth Factors
  • Interleukin-6
  • Ly6a protein, mouse
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Proto-Oncogene Proteins c-kit