Granulocyte-macrophage colony stimulating factor and interleukin-3 regulate the production of an interleukin-1 inhibitor by the differentiated AML-193 leukemic cell line.
Treatment of the AML-193 leukemic cell line with phorbol myristate acetate (PMA) resulted in the loss of their ability to proliferate in response to GM-CSF or IL-3. This was not due to a change in number or affinity of GM-CSF receptors, but possibly resulted from an other cellular mechanism. The AML-193 differentiated cells acquired the ability to phagocytose glutaraldehyde-fixed E.coli in a similar fashion to mature macrophages. In addition the PMA-differentiated AML-193 cells now secreted a factor which specifically inhibited the binding of interleukin-1 (IL-1) to its receptor on the murine thymoma cell line EL-4.6.1C10. The synthesis of this inhibitor was further increased by the addition of GM-CSF or IL-3. Pulse labelling experiments showed that this activity was due to a 26 kDa protein that bound to the IL-1 receptor even in the presence of neutralizing antibodies against IL-1 alpha or IL-1 beta, and this binding was only antagonized by IL-1 alpha or IL-1 beta. In contrast, peripheral monocytes obtained from the blood of normal donors, when induced with either GM-CSF or IL-3, produced large quantities of inhibitor in the absence of PMA. This report clearly shows that a leukaemic cell line can respond to GM-CSF and IL-3 in different ways before and after in vitro differentiation.
Kindler
V
V
Glaxo Institute for Molecular Biology S.A., Geneva, Switzerland.
Shields
J
J
Ayer
D
D
Benotto
W
W
Mazzei
G J
GJ
D000818:Animals; D001667:Binding, Competitive; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology*; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013945:Thymoma / Q000473:pathology; D013953:Thymus Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D007377:Interleukin-3; D007378:Interleukins; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate