Tumor necrosis factor-alpha (TNF-alpha) potently enhances in vitro macrophage production from primitive murine hematopoietic progenitor cells in combination with stem cell factor and interleukin-7: novel stimulatory role of p55 TNF receptors.
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.
Fahlman
C
C
Department of Immunology, Norwegian Radium Hospital, Montebello.
Jacobsen
F W
FW
Veiby
O P
OP
McNiece
I K
IK
Blomhoff
H K
HK
Jacobsen
S E
SE
D000818:Animals; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D016298:Hematopoietic Cell Growth Factors; D015851:Interleukin-7; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha