Lymphotoxin and TNF differ greatly in capacity to induce differentiation of human myeloblastic leukemia ML-1 cells.
We found that recombinant and natural lymphotoxin differ from TNF in that they only marginally induce differentiation of human myeloblastic leukemia ML-1 cells. Even at 1,000-fold concentrations, lymphotoxin was significantly less potent than TNF. Lymphotoxin competitively, but not completely, inhibited TNF-induced differentiation. Based on studies of the two types of TNF receptors (55 kDa and 75 kDa) using monoclonal antibodies, the binding activity of lymphotoxin to the receptors was less than 1/3 that of TNF, but lymphotoxin could bind to both TNF receptors. Both receptors were involved in induction of differentiation by TNF. However, lymphotoxin, differed from TNF; it seemed to be weak in sending signals for differentiation through the 75 kDa receptor.
Takeda
K
K
1st Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
Iwamoto
S
S
Takeda
M
M
D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha