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. 1994 Apr 15;299(Pt 2):553–559. doi: 10.1042/bj2990553

Dexamethasone modifies the functional responses of the granulocytic differentiating HL-60 cells.

D Collado-Escobar 1, F Mollinedo 1
PMCID: PMC1138307  PMID: 7909661

Abstract

We have studied the effect of dexamethasone on the granulocytic differentiation of the human promyelocytic cell line HL-60 induced by treatment with retinoic acid (RA) or dimethyl sulphoxide (DMSO). Dexamethasone potentiated the immunophenotypic and functional parameters associated with the granulocytic differentiation induced by RA, including changes in CD11b and CD71 expression, inhibition of cell proliferation, enhancement of secretory and oxidative responses and increase of the phospholipase C (PLC), phospholipase A2 (PLA2) and phospholipase D (PLD) activities. However, dexamethasone had selective effects on several parameters of DMSO-induced cell differentiation. Dexamethasone inhibited the DMSO-induced increase of CD11b cell surface expression as well as the oxidative response and PLD activation triggered by 4 beta-phorbol 12-myristate 13-acetate. Nevertheless, dexamethasone potentiated the receptor-mediated PLC activation and the receptor-mediated secretory and oxidative responses in DMSO-treated cells. Unlike RA-treated HL-60 cells, the DMSO-treated cells contained high values of activatable PLA2 activity which were not affected by dexamethasone. Thus dexamethasone affected differently functional parameters and effector systems of granulocytic HL-60 cells, depending on the differentiation agent used. Dexamethasone by itself did not induce HL-60 cell differentiation, but enhanced the receptor- and non-receptor-mediated secretory responses and induced the appearance of stimulated PLA2 activity in undifferentiated HL-60 cells. These data provide evidence for the selective modulation of functional responses by dexamethasone through alterations in signalling processes.

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Selected References

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  1. Bass D. A., Parce J. W., Dechatelet L. R., Szejda P., Seeds M. C., Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol. 1983 Apr;130(4):1910–1917. [PubMed] [Google Scholar]
  2. Bellavite P., Corso F., Dusi S., Grzeskowiak M., Della-Bianca V., Rossi F. Activation of NADPH-dependent superoxide production in plasma membrane extracts of pig neutrophils by phosphatidic acid. J Biol Chem. 1988 Jun 15;263(17):8210–8214. [PubMed] [Google Scholar]
  3. Birnie G. D. The HL60 cell line: a model system for studying human myeloid cell differentiation. Br J Cancer Suppl. 1988 Dec;9:41–45. [PMC free article] [PubMed] [Google Scholar]
  4. Bonser R. W., Thompson N. T., Randall R. W., Garland L. G. Phospholipase D activation is functionally linked to superoxide generation in the human neutrophil. Biochem J. 1989 Dec 1;264(2):617–620. doi: 10.1042/bj2640617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buyon J. P., Korchak H. M., Rutherford L. E., Ganguly M., Weissmann G. Female hormones reduce neutrophil responsiveness in vitro. Arthritis Rheum. 1984 Jun;27(6):623–630. doi: 10.1002/art.1780270604. [DOI] [PubMed] [Google Scholar]
  6. Chang F. H., Bourne H. R. Dexamethasone increases adenylyl cyclase activity and expression of the alpha-subunit of Gs in GH3 cells. Endocrinology. 1987 Nov;121(5):1711–1715. doi: 10.1210/endo-121-5-1711. [DOI] [PubMed] [Google Scholar]
  7. Clark R. A., Leidal K. G., Pearson D. W., Nauseef W. M. NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxide-generating system. J Biol Chem. 1987 Mar 25;262(9):4065–4074. [PubMed] [Google Scholar]
  8. Cockcroft S. G-protein-regulated phospholipases C, D and A2-mediated signalling in neutrophils. Biochim Biophys Acta. 1992 Aug 14;1113(2):135–160. [PubMed] [Google Scholar]
  9. Cockcroft S., Stutchfield J. The receptors for ATP and fMetLeuPhe are independently coupled to phospholipases C and A2 via G-protein(s). Relationship between phospholipase C and A2 activation and exocytosis in HL60 cells and human neutrophils. Biochem J. 1989 Nov 1;263(3):715–723. doi: 10.1042/bj2630715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collado-Escobar D., Cunha-Melo J. R., Beaven M. A. Treatment with dexamethasone down-regulates IgE-receptor-mediated signals and up-regulates adenosine-receptor-mediated signals in a rat mast cell (RBL-2H3) line. J Immunol. 1990 Jan 1;144(1):244–250. [PubMed] [Google Scholar]
  11. Collins S. J. The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression. Blood. 1987 Nov;70(5):1233–1244. [PubMed] [Google Scholar]
  12. Collins S., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids. J Biol Chem. 1988 Jul 5;263(19):9067–9070. [PubMed] [Google Scholar]
  13. Costa-Casnellie M. R., Segel G. B., Cragoe E. J., Jr, Lichtman M. A. Characterization of the Na+/H+ exchanger during maturation of HL-60 cells induced by dimethyl sulfoxide. J Biol Chem. 1987 Jul 5;262(19):9093–9097. [PubMed] [Google Scholar]
  14. Crabtree G. R., Munck A., Smith K. A. Glucocorticoids inhibit expression of Fc receptors on the human granulocytic cell line HL-60. Nature. 1979 May 24;279(5711):338–339. doi: 10.1038/279338a0. [DOI] [PubMed] [Google Scholar]
  15. Dewald B., Thelen M., Baggiolini M. Two transduction sequences are necessary for neutrophil activation by receptor agonists. J Biol Chem. 1988 Nov 5;263(31):16179–16184. [PubMed] [Google Scholar]
  16. Hirata F., Schiffmann E., Venkatasubramanian K., Salomon D., Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci U S A. 1980 May;77(5):2533–2536. doi: 10.1073/pnas.77.5.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ho P. T., Ishiguro K., Sartorelli A. C. Regulation of transferrin receptor in myeloid and monocytic differentiation of HL-60 leukemia cells. Cancer Res. 1989 Apr 15;49(8):1989–1995. [PubMed] [Google Scholar]
  18. Hoff T., Spencker T., Emmendoerffer A., Goppelt-Struebe M. Effects of glucocorticoids on the TPA-induced monocytic differentiation. J Leukoc Biol. 1992 Aug;52(2):173–182. doi: 10.1002/jlb.52.2.173. [DOI] [PubMed] [Google Scholar]
  19. Keizer G. D., Borst J., Figdor C. G., Spits H., Miedema F., Terhorst C., De Vries J. E. Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. Eur J Immunol. 1985 Nov;15(11):1142–1148. doi: 10.1002/eji.1830151114. [DOI] [PubMed] [Google Scholar]
  20. Kobayashi M., Bansal V. S., Singh I., Kanfer J. N. Dexamethasone-induced reduction of phospholipase D activity in the rat. Possible role of lipocortin. FEBS Lett. 1988 Aug 29;236(2):380–382. doi: 10.1016/0014-5793(88)80060-7. [DOI] [PubMed] [Google Scholar]
  21. Koeffler H. P., Golde D. W., Lippman M. E. Glucocorticoid sensitivity and receptors in cells of human myelogenous leukemia lines. Cancer Res. 1980 Mar;40(3):563–566. [PubMed] [Google Scholar]
  22. Makowske M., Ballester R., Cayre Y., Rosen O. M. Immunochemical evidence that three protein kinase C isozymes increase in abundance during HL-60 differentiation induced by dimethyl sulfoxide and retinoic acid. J Biol Chem. 1988 Mar 5;263(7):3402–3410. [PubMed] [Google Scholar]
  23. Mishler J. M., Emerson P. M. Development of Neutrophilia by serially increasing doses of dexamethasone. Br J Haematol. 1977 Jun;36(2):249–257. doi: 10.1111/j.1365-2141.1977.tb00646.x. [DOI] [PubMed] [Google Scholar]
  24. Mollinedo F., Burgaleta C., Velasco G., Arroyo A. G., Acevedo A., Barasoain I. Enhancement of human neutrophil functions by a monoclonal antibody directed against a 19-kDa antigen. J Immunol. 1992 Jul 1;149(1):323–330. [PubMed] [Google Scholar]
  25. Mollinedo F., Gajate C., Schneider D. L. Cytochrome b co-fractionates with gelatinase-containing granules in human neutrophils. Mol Cell Biochem. 1991 Jun 26;105(1):49–60. doi: 10.1007/BF00230374. [DOI] [PubMed] [Google Scholar]
  26. Mollinedo F., Gajate C., Tugores A., Flores I., Naranjo J. R. Differences in expression of transcription factor AP-1 in human promyelocytic HL-60 cells during differentiation towards macrophages versus granulocytes. Biochem J. 1993 Aug 15;294(Pt 1):137–144. doi: 10.1042/bj2940137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mollinedo F. Isolation of human neutrophil plasma membranes employing neutrophil cytoplasts and changes in the cell-surface proteins upon cell activation. Biochim Biophys Acta. 1986 Sep 25;861(1):33–43. doi: 10.1016/0005-2736(86)90368-8. [DOI] [PubMed] [Google Scholar]
  28. Nakamura T., Kharbanda S., Spriggs D., Kufe D. Effects of dexamethasone on induction of monocytic differentiation in human U-937 cells by dimethylsulfoxide. J Cell Physiol. 1990 Feb;142(2):261–267. doi: 10.1002/jcp.1041420207. [DOI] [PubMed] [Google Scholar]
  29. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
  30. Olsson I., Olofsson T. Induction of differentiation in a human promyelocytic leukemic cell line (HL-60). Production of granule proteins. Exp Cell Res. 1981 Jan;131(1):225–230. doi: 10.1016/0014-4827(81)90422-5. [DOI] [PubMed] [Google Scholar]
  31. Pai J. K., Siegel M. I., Egan R. W., Billah M. M. Activation of phospholipase D by chemotactic peptide in HL-60 granulocytes. Biochem Biophys Res Commun. 1988 Jan 15;150(1):355–364. doi: 10.1016/0006-291x(88)90528-1. [DOI] [PubMed] [Google Scholar]
  32. Petroni K. C., Shen L., Guyre P. M. Modulation of human polymorphonuclear leukocyte IgG Fc receptors and Fc receptor-mediated functions by IFN-gamma and glucocorticoids. J Immunol. 1988 May 15;140(10):3467–3472. [PubMed] [Google Scholar]
  33. Roberts P. J., Cross A. R., Jones O. T., Segal A. W. Development of cytochrome b and an active oxidase system in association with maturation of a human promyelocytic (HL-60) cell line. J Cell Biol. 1982 Dec;95(3):720–726. doi: 10.1083/jcb.95.3.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rodan S. B., Rodan G. A. Dexamethasone effects on beta-adrenergic receptors and adenylate cyclase regulatory proteins Gs and Gi in ROS 17/2.8 cells. Endocrinology. 1986 Jun;118(6):2510–2518. doi: 10.1210/endo-118-6-2510. [DOI] [PubMed] [Google Scholar]
  35. Sanchez-Madrid F., Toribio M. L., Gambón F., de Landazuri M. O. Cell surface molecular changes on the activation of human thymocytes. J Immunol. 1985 Dec;135(6):3938–3943. [PubMed] [Google Scholar]
  36. Scher W., Tsuei D., Sassa S., Price P., Gabelman N., Friend C. Inhibition of dimethyl sulfoxide-stimulated Friend cell erythrodifferentiation by hydrocortisone and other steroids. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3851–3855. doi: 10.1073/pnas.75.8.3851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Seifert R., Burde R., Schultz G. Activation of NADPH oxidase by purine and pyrimidine nucleotides involves G proteins and is potentiated by chemotactic peptides. Biochem J. 1989 May 1;259(3):813–819. doi: 10.1042/bj2590813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Skubitz K. M., Zhen Y. S., August J. T. Dexamethasone synergistically induces chemotactic peptide receptor expression in HL-60 cells. Blood. 1982 Mar;59(3):586–593. [PubMed] [Google Scholar]
  39. Smith R. J., Iden S. S. Pharmacological modulation of chemotactic factor-elicited release of granule-associated enzymes from human neutrophils. Effects of prostaglandins, nonsteroid anti-inflammatory agents and corticosteroids. Biochem Pharmacol. 1980 Sep 1;29(17):2389–2395. doi: 10.1016/0006-2952(80)90274-9. [DOI] [PubMed] [Google Scholar]
  40. Stone R. M., Imamura K., Datta R., Sherman M. L., Kufe D. W. Inhibition of phorbol ester-induced monocytic differentiation and c-fms gene expression by dexamethasone: potential involvement of arachidonic acid metabolites. Blood. 1990 Sep 15;76(6):1225–1232. [PubMed] [Google Scholar]
  41. Stutchfield J., Cockcroft S. Guanine nucleotides stimulate polyphosphoinositide phosphodiesterase and exocytotic secretion from HL60 cells permeabilized with streptolysin O. Biochem J. 1988 Mar 1;250(2):375–382. doi: 10.1042/bj2500375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Suda T., Miura Y., Ijima H., Ozawa K., Motoyoshi K., Takaku F. The effect of hydrocortisone on human granulopoiesis in vitro with cytochemical analysis of colonies. Exp Hematol. 1983 Feb;11(2):114–121. [PubMed] [Google Scholar]
  43. Umeki S., Soejima R. Hydrocortisone inhibits the respiratory burst oxidase from human neutrophils in whole-cell and cell-free systems. Biochim Biophys Acta. 1990 Apr 9;1052(1):211–215. doi: 10.1016/0167-4889(90)90078-r. [DOI] [PubMed] [Google Scholar]

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