Expression and role in growth regulation of tumour necrosis factor receptors p55 and p75 in acute myeloblastic leukaemia cells.
Tumour necrosis factor (TNF)-alpha exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-alpha-driven growth regulation of AML blasts in vitro. Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-alpha-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-alpha-induced autocrine growth. In contrast, the TNF-alpha-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-alpha on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-alpha-signalled growth inhibition is exclusively transduced via TNF-Rp55.
Carter
A
A
Department of Haematology, Technion-Israel Institute of Technology, Haifa, Israel.
Haddad
N
N
Draxler
I
I
Israeli
E
E
Raz
B
B
Rowe
J M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D005260:Female; D005455:Fluorescent Antibody Technique; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology
D015703:Antigens, CD; D004273:DNA, Neoplasm; D007377:Interleukin-3; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor