Summary
Variations in the (2′–5′) oligoadenylate synthetase (2–5 A synthetase) level were examined prior to and during the differentiation in culture of the human monocyte cell line U937 and the promyelocytic cell line HL60 in an attempt to reveal whether the enzyme is actively involved in hematopoietic cell maturation. The basal level of this enzyme was much higher in U937 than in HL60 cells. The activity of 2–5 A synthetase was enhanced in both cell lines in response to α, β interferons.
During cell differentiation, ten markers were measured. The level of the enzyme rose during the process of cellular maturation in both cell lines. The 2–5 A synthetase activity observed in differentiated HL60 and U937 cells was comparable to that observed in mature normal granulocytes and monocytes respectively. Induction of U937 differentiation by chemicals was associated with detectable production of IFN. The increase in enzyme activity observed was mostly dependent on endogenous production of interferon, since it was inhibited by interferon antibodies. Kinetic studies showed that in U937 cells 2–5 A synthetase was expressed prior to several of the differentiation markers. The rise in the enzyme's level observed during the differentiation of HL60 cells was independent of endogenous production of interferon, since it was not inhibited by the addition of anti-interferon antibodies.
These results suggest that different biochemical and molecular mechanisms are responsible for the induction of 2–5 A synthetase observed during the differentiation of hematopoietic cells. In any case, 2–5 A synthetase can be considered as a biochemical marker of cell status and differentiation in hematopoietic cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- 2−5 A synthetase:
-
(2′5′) oligoadenylate synthetase
- TPA:
-
12-0-tetra-decanoyl-phorbol-l3-acetate
- Hydroxyvit D3:
-
1.25 diHydroxyvitamin D3
- DMSO:
-
Dimethylsulfoxide
- NBT:
-
Nitroblue-tetrazolium
- MAS 067, MAS 072, MO2 :
-
monoclonal antibodies
- IFN:
-
interferon
References
Lengyel P: Biochemistry of interferons and their actions. Ann Rev Biochem 51:251–282, 1982.
Hovanessian AG, Kerr IM: Synthesis of an oligonucleotide inhibitor of protein synthesis in rabbit reticulocyte lysates analogous to that formed in extracts from interferon treated cells. Eur J Biochem 84:149–159, 1978.
Silverman RH, Cayley PJ, Knight M, Gilbert CS, Kerr IM: Control of the ppp (A2′p)nA system in HeLa cells. Eur J Biochem 124:131–138, 1982.
Baglioni C, Minks MA, Maroney PA: Interferon action may be mediated by activation of a nuclease by ppp A2′p5′A2′p5′A. Nature (London) 273:684–687, 1978.
Ferbus D, Justesen J, Bertrand H, Thang MN: (2′–5′) oligoadenylate synthetase in the maturation of rabbit reticulocytes. Mol Cell Biochem 62: 51–55, 1984.
Stark GR, Dower WJ, Schimke RT, Brown RE, Kerr IM: ppp A2′p5′A2′p5′A synthetase: convenient assay, species and tissue distribution and variation upon withdrawal of estrogen from chick oviducts. Nature 278:471–473, 1979.
Quesenberry PJ: Hemopoietic stem cells. In William WJ, Beutler E, Erskev AJ, Lichtman MA, Mc Grew-Hill (eds), Hematology, New York Publ 1983, p. 129.
Collins SJ, Gallo RC, Gallagher RE: Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature 270:347–349, 1977.
Sundstrom C, Nilsson K: Establishment and characterisation of a human lymphoma cell line. Int J Cancer 17:565–577, 1976.
Vainchenker W, Testa U, Deschamps JF, Henri A, Titeux M, Breton-Gorius J, Rochant H, Lee D, Cartron JP: Clonal expression of the Tn Antigen in erythroid and granulocyte colonies and its application to determination of the clonality of the human megakaryocyte colony assay. J Clint Invest 69:1081–1091, 1982.
Lotem J, Sachs L: Induction of specific changes in the surface membrane of Myeloid leukemic cells by steroid hormones. Int J Cancer 15:731–740, 1975.
Todd RF, Schlossman SF: Analysis of antigenic determinants on human monocytes and macrophages. Blood. 59:775–786, 1982.
Tanaka H, Abe E, Miyaura C, Shiina Y, Suda T: 1α25-Dihydroxyvitamin D3 induces differentiation of human promyelocytic leukemia cells (HL-60) into monocyte-macrophages, but not into granulocytes. BBRC 11:86–92, 1983.
Nerurkar LS: Lysozyme. In: Adams DO, Edelson PJ, Koren H (eds). Methods for studying mononuclear phagocytes. Academic Press, New York Publ p 667–783, 1981.
Johnston RB: Secretion of superoxide anion. In: Adams DO, Edelson PJ, Koren H (eds). Methods for studying mononuclear phagocytes. Academic Press, New York Publ. p 489–497, 1981.
Baggiolini M, Hirsch JG, Deduve C: Resolution of granules from rabbit heterophil leukocytes into distinct populations by zonal sedimentation. J Cell Biol 40:529–541, 1969.
Justesen J, Ferbus D, Thang MN: Elongation mechanism and substrate specificity of 2′5′ oligo-adenylate synthetase. Proc Nat] Acad Sci USA 77:4618–4622, 1980.
Spector T: Raffinement of the coomassie blue method on protein quantitation. Anal Biochem 86:142–146, 1978.
Dodd RC, Cohen MS, Newman SL, Gray TK: Vitamin D metabolites change the phenotype of monoblastic U937 cells. Proc Natl Acad Sci USA 80:7538–7541, 1983.
Yarden A, Gottlieb HS, Chebath J, Revel M, Kimchi A: Autogenous production of interferon-β3 switches on HLA genes during differentiation of Histiocytic lymphoma U937 cells. EMBO J 3:969–973, 1984.
Rovera GD, Santoli C, Dansky C: Human promyelocytic leukemia cells in culture differentiates into macrophage like cells when treated with phorbol ester. Proc Natl Acad Sci USA 76:2779–2785, 1979.
Tanaka H, Abe E, Miyaura C, Shiina Y, Suda T: 1α, 25 diHydroxyvitamin D3 induces differentiation of Human Promyelocytic Leukemia cells (HL60) into monocyte-Macrophages, but not granulocytes. Biochem Biophys Res Comm 117:86, 1983.
Koeffler HP: Induction of human acute myelogenous leukemia cells: therapeutic implication. Blood 62:709–721, 1983.
Kimchi A: Increased levels of interferon-induced (2′–5′) oligo-isoadenylate in Mature T lymphocytes and in differenciated Friend-erythroleukemic cells. J Interferon Res 1:559–569, 1981.
Friedman-Einat M, Revel M, Kimchi A: Initial characterisation of a spontaneous interferon secreted during growth and differentiation of Friend erythroleukemia cells. Mol Cell Biol 2:1472–1480, 1982.
Mechti N, Affabris E, Romeo G, Lebleu B, Rossi GB: Role of interferon and 2′–5′ oligoadenylate synthetase in Erythroid differentiation of Friend leukemia cells. J Biol Chem 259:3261–3265, 1984.
Sokawa Y, Nagata K, Ichikawa Y: Induction and function of 2′–5′ oligoadenylate synthetase in differentiation of mouse Myeloid Leukemia cells. Exp Cell Res 135:191–197, 1981.
Besançon F, Bourgeade MF, Justesen J, Ferbus D, Thang MN: Two inducers of cell differentiation enhance the 2′–5′ oligoadenylate synthetase activity in MSV transformed cells. Biochem Biophys Res Commun 103:16–24, 1981.
Bourgeade MF, Besançon F: Induction of 2′–5′ oligodenylate synthetase by retinoic acid in two human transformed cell lines. Cancer Res. 44:5355, 1984.
Hattori T, Pack M, Bougnoux P, Chang L, Hoffman T: Interferon-induced differentiation of U937 cells. J Clin Invest 72:237–244, 1983.
Ralph P, Harris PE, Punjabi CJ, Welte K, Litcofsky PB, Ho MK, Rubin BY, Moore MAS, Springer TA: Lymphokine inducing ‘terminal differentiation’ of the human monoblast leukemia line U937: a role for γ interferon. Blood 62: 1169–1175, 1983.
Schmidt A, Hattori T, Hoffman T: Differentiation of a human monocyte-like cell line by (2′–5′) oligoisoadenylate. Exp Cell Res 150:292–297, 1984.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ferbus, D., Testa, U., Titeux, M. et al. Induction of (2′–5′) oligoadenylate synthetase activity during granulocyte and monocyte differentiation. Mol Cell Biochem 67, 125–133 (1985). https://doi.org/10.1007/BF02370171
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02370171