Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Stem cell factor (SCF), a key regulator of hematopoiesis, potently synergizes with a number of hematopoietic growth factors. However, little is known about growth factors capable of inhibiting the actions of SCF. TNF-alpha has been shown to act as a bidirectional regulator of myeloid cell proliferation and differentiation. This study was designed to examine interactions between TNF-alpha and SCF. Here, we demonstrate that TNF-alpha potently and directly inhibits SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells. Furthermore, TNF-alpha blocked all colony formation stimulated by SCF in combination with granulocyte colony-stimulating factor (CSF) or CSF-1. The synergistic effect of SCF observed in combination with GM-CSF or IL-3 was also inhibited by TNF-alpha, resulting in colony numbers similar to those obtained in the absence of SCF. These effects of TNF-alpha were mediated through the p55 TNF receptor, whereas little or no inhibition was signaled through the p75 TNF receptor. Finally, TNF-alpha downregulated c-kit cell-surface expression on CD34+ bone marrow cells, and this was predominantly a p55 TNF receptor-mediated event as well.

Original publication

DOI

10.1172/JCI117303

Type

Journal article

Journal

J Clin Invest

Publication Date

07/1994

Volume

94

Pages

165 - 172

Keywords

Adult, Antigens, CD, Antigens, CD34, Bone Marrow Cells, Cell Division, Hematopoietic Cell Growth Factors, Hematopoietic Stem Cells, Humans, Interleukin-3, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-kit, Receptor Protein-Tyrosine Kinases, Receptors, Colony-Stimulating Factor, Receptors, Tumor Necrosis Factor, Stem Cell Factor, Tumor Necrosis Factor-alpha