Opposite sensitivity to the antiproliferative action of interferon-alpha and granulocyte-macrophage colony-stimulating factor in monoblastic U937 cells.
Three variants of the human monoblastic cell line U937 with different degrees of sensitivity to the antiproliferative action of interferon-alpha (IFN-alpha were examined for phenotypic differences. The highly IFN-sensitive variant U937-V expressed twice as many IFN-alpha binding sites as both its IFN-alpha-resistant derivative U937-VR and the cell line U937 exhibiting a 20-fold reduction in IFN-alpha sensitivity as compared to U937-V cells. All three variants were IFN-reactive with regard to induction of 2',5'-oligoadenylate (2-5A) synthetase activity and were similarly sensitive to the growth-inhibiting action of IFN-gamma and tumor necrosis factor. Responsiveness to the antiproliferative effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), however, was confined to cell lines U937 and U937-VR. Although expressing a comparable number of GM-CSF receptors, the highly IFN-sensitive variant U937-V was refractory to GM-CSF. Flow cytometry revealed a marked difference in the expression of the antigen CD11b which was detectable on 85% of cells of the U937-V line but only on approximately 25% of cells derived from the U937 and U937-VR lines. Results thus demonstrate opposite sensitivity of U937 cells to the growth-inhibiting action of IFN-alpha and GM-CSF, apparently dependent on the state of U937 differentiation as determined by expression of the CD11b antigen.
Kloke
O
O
Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen Medical School.
Moritz
T
T
Kummer
G
G
Hust
H
H
Ross
B
B
Seeber
S
S
Niederle
N
N
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy*; D010641:Phenotype; D011485:Protein Binding; D017471:Receptors, Interferon / Q000378:metabolism; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016898:Interferon-alpha; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015088:2',5'-Oligoadenylate Synthetase