Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Tumor necrosis factor-alpha (TNF-alpha) is a bifunctional regulator of hematopoiesis, and its cellular responses are mediated by two distinct cell surface receptors. TNF-alpha generally inhibits the growth of primitive murine hematopoietic progenitor cells (Lin-Scal+) in response to multiple cytokine combinations, and the p75 TNF receptor is essential in signaling such inhibition. In the present study we show the reverse phenomenon in that TNF-alpha on the same progenitor cell population in combination with stem cell factor (SCF) and interleukin-7 (IL-7) through the p55 TNF receptor can recruit additional progenitors to proliferate. In contrast, TGF-beta 1, another bifunctional regulator of hematopoietic progenitor cell growth, completely blocked SCF plus IL-7-induced proliferation. TNF-alpha increased the number of responding progenitors, as well as the size of the colonies formed. The synergistic effects of TNF-alpha were seen at the single cell level, suggesting that its effects are directly mediated. Finally, whereas SCF plus IL-7 promoted primarily granulopoiesis, the addition of TNF-alpha switched the differentiation toward the production of almost exclusively macrophages.

Type

Journal article

Journal

Blood

Publication Date

01/09/1994

Volume

84

Pages

1528 - 1533

Keywords

Animals, Bone Marrow Cells, Cell Adhesion Molecules, Cell Differentiation, Cell Division, Cells, Cultured, Dose-Response Relationship, Drug, Drug Synergism, Hematopoietic Cell Growth Factors, Hematopoietic Stem Cells, Humans, Interleukin-7, Kinetics, Macrophages, Mice, Mice, Inbred C57BL, Rats, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Stem Cell Factor, Tumor Necrosis Factor-alpha