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Signal Transduction

Modifications in phospholipase D activity and isoform expression occur upon maturation and differentiation in vivo and in vitro in human myeloid cells

Leukemia volume 14, pages 2118–2127 (2000)Cite this article

Abstract

Activation of phospholipase D (PLD) occurs in response to various stimuli and results from the activity of two isozymes, hPLD1 and hPLD2. PLD activity appears to be involved in several myeloid cell processes during their development and activation, including proliferation of myeloblasts in the bone marrow and secretion, phagocytosis and NADPH oxidase activation, essential functions of differentiated neutrophils. The present work studies PLD characteristics, activity and both isozyme expression during maturation and differentiation of myeloid cells by using three different systems: leukemic myeloblasts at different stages of maturation, terminally differentiated neutrophils ex vivo and four human myeloid cell lines, NB4, HL-60, PLB 985 and U937, induced to differentiate with all-trans retinoic acid (ATRA), a cyclic adenosine monophosphate (cAMP) analogue or both agents together. HL-60, a bipotential cell line has also been differentiated along the granulocytic pathway with DMSO and the monocytic pathway with 1,25-dihydroxy vitamin D3. In all these systems, PLD activity increases with maturation and differentiation whatever the inducer used and the granulocytic or monocytic pathways. Increase in basal activity which reflects the expression during development of both hPLD1 and hPLD2 appears to be mainly related to the former isozyme expression. Association of PLD characteristic changes with maturation and differentiation was also confirmed using two NB4 clones resistant to these processes. Comparison between PLD characteristics in myeloblasts during maturation and differentiation ex vivo and in vitro in the different cell lines demonstrated that NB4 induced to differentiate with ATRA represents the best model for further studies on the specific roles of each PLD isoform in various functions of differentiated myeloid cells.

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References

  1. Ali H, Haribabu B, Richardson RM, Snyderman R . Mechanisms of inflammation and leukocyte activation Adv Rheumatol 1997 81: 1–28

    CAS  Google Scholar 

  2. Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R Fenaux P, Degos L . All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia: I. clinical results Blood 1990 76: 1704–1709

    Article  CAS  Google Scholar 

  3. Fenaux P, Castaigne S, Dombret H, Archimbaud, E, Duarte M, Morel P, Lamy T, Tilly H, Guerci A, Maloisel F, Bordessoule D, Sadoun A, Tiberghein P, Fegueux N, Daniel M-T, Chomienne C, Degos L . All-trans retinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remission in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases Blood 1992 80: 2176–2181

    Article  CAS  Google Scholar 

  4. Liscovitch M, Czarny M, Fiucci G, Tang X . Phospholipase D: molecular and cell biology of a novel gene family Biochem J 2000 345: 401–415

    Article  CAS  PubMed  Google Scholar 

  5. English D, Cui Y, Siddiqui RA . Messenger functions of phosphatidic acid Chem Phys Lipids 1996 80: 117–132

    Article  CAS  Google Scholar 

  6. Hammond SM, Altshuller YM, Sung T-C, Rudge SA, Rose K, Engebrecht J, Morris AJ, Frohman MA . Human ADP-ribosylation activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family J Biol Chem 1995 270: 29640–29643

    Article  CAS  Google Scholar 

  7. Lopez I, Arnold RS, Lambeth JD . Cloning and initial characterization of a human phospholipase D2 (hPLD2) J Biol Chem 1998 273: 12846–12852

    Article  CAS  Google Scholar 

  8. Colley WC, Altshuller YM, Sue-Ling CK, Copeland NG, Gilbert DJ, Jenkins NA, Branch KD, Tsirka SE, Bollag RJ, Bollag WB, Frohman MA . Cloning and expression analysis of murine phospholipase D1 Biochem J 1997 326: 745–753

    Article  CAS  PubMed  Google Scholar 

  9. Park S-K, Provost JJ, Bae CD, Ho W-T, Exton JH . Cloning and characterization of phospholipase D from rat brain J Biol Chem 1997 272: 29263–29271

    Article  CAS  Google Scholar 

  10. Dalton WT, Aheearn M, McCredie K, Freidreich EJ, Stass SA, Trujillo JM . HL60 cell line was derived from a patient with FAB-M2 and not FAB-M3 Blood 1988 71: 242–247

    Article  Google Scholar 

  11. Lanotte M, Martin-Thouvenin V, Najman S, Ballerini P, Valensi F, Berger R . NB4, a maturation inducible cell line with t(15/17) marker isolated from a human acute promyelocytic leukemia (M3) Blood 1990 77: 1080–1086

    Article  Google Scholar 

  12. Breitman TR, Selonick SE, Collins SJ . Induction of differentiation of the human promelocytic leukemia cell line (HL-60) by retinoic acid Proc Natl Acad Sci USA 1980 77: 2936–2940

    Article  CAS  Google Scholar 

  13. Chaplinski TJ, Niedel JE . Cyclic nucleotide-induced maturation of human promyelocytic leukemia cells J Clin Invest 1982 70: 953–964

    Article  CAS  PubMed  Google Scholar 

  14. Geny B, Cockcroft S . Synergistic activation of phospholipase D by protein kinase C- and G-protein-mediated pathways in streptolysin O-permeabilized HL-60 cells Biochem J 1992 284: 531–538

    Article  CAS  PubMed  Google Scholar 

  15. Marcil J, Harbour D, Naccache PH, Bourgoin S . Human phospholipase D1 can be tyrosine phosphorylated in HL-60 granulocytes J Biol Chem 1997 272: 20660–20664

    Article  CAS  Google Scholar 

  16. Ruchaud S, Duprez E, Gendron MC, Houge G, Genieser HG, Jastorff B, Doskeland SO, Lanotte M . Two distinctly regulated events, priming and triggering, during retinoic-induced maturation and resistance of NB4 promyelocytic leukemia cell line Proc Natl Acad Sci USA 1994 91: 8428–8432

    Article  CAS  Google Scholar 

  17. Duprez E, Benoit G, Flexor M, Lillehaug JR, Lanotte M . A mutated PML/RARA found in the retinoid maturation resistant NB4 subclone NB4-R2, blocks RARA and wild-type PML/RARA transcriptional activities Leukemia 2000 14: 255–261

    Article  CAS  Google Scholar 

  18. Warrell RPJ, Frankel SR, Miller WH Jr, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreeff M, Tafuri A, Jakubowski A, Gabrilove J, Gordon M, Dmitrovsky, E . Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans retinoic acid) New Engl J Med 1991 324: 1385–1393

    Article  Google Scholar 

  19. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY . Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia Blood 1988 72: 567–572

    Article  CAS  Google Scholar 

  20. Nakashima S, Ohguchi K, Frohman MA, Nozawa Y . Increased mRNA expression of phospholipase D (PLD) isozymes during granulocytic differentiation of HL60 cells Biochim Biophys Acta 1998 1389: 173–177

    Article  CAS  Google Scholar 

  21. Zhao D, Berse B, Holler T, Cermak JM, Blusztajn JK . Developmental changes in phospholipase D activity and mRNA levels in rat brain Dev Brain Res 1998 109: 121–127

    Article  CAS  Google Scholar 

  22. Griner RD, Quin F, Jung E, Sue-Ling CK, Crawford KB, Mann-Blakeney R, Bollag RJ, Bollinger Bollag W . 1,25-dihydroxyvitamin D3 induces phospholipase D-1 expression in primary mouse epidermal keratinocytes J Biol Chem 1999 274: 4663–4670

    Article  CAS  Google Scholar 

  23. Hayakawa K, Nakashima S, Ito Y, Mizuta K, Miyata H, Nozawa Y . Increased expression of phospholipase D1 mRNA during cAMP- or NGF-induced differentition in PC12 cells Neurosci Lett 1999 265: 127–130

    Article  CAS  Google Scholar 

  24. Yoshimura S-I, Nakashima S, Ohguchi K, Sakai H, Shinoda J, Sakai N, Nozawa Y . Differential mRNA expression of phospholipase D (PLD) isozymes during cAMP-induced differentiation in C6 glioma cells Biochem Biophys Res Commun 1996 225: 494–499

    Article  CAS  Google Scholar 

  25. Min DS, Shin KS, Kim E-G, Kim SR, Yoon SH, Kim M-S, Jo Y-H . Down-regulation of phospholipase D during differentiation of mouse F9 teratocarcinoma cells FEBS Lett 1999 454: 197–200

    Article  CAS  Google Scholar 

  26. Moritz A, De Graan PNE, Gispen WH, Wirtz KWA . Phosphatidic acid is a specific activator of phosphatidylinositol-4-phosphate kinase J Biol Chem 1992 267: 7207–7210

    CAS  Google Scholar 

  27. Jenkins GH, Fisette PL, Anderson RA . Type I phosphatidylinositol 4-phosphate 5 kinase isoforms are specifically stimulated by phosphatidic acid J Biol Chem 1994 269: 11547–11554

    CAS  Google Scholar 

  28. Liscovitch M, Chalifa V, Pertile P, Chen C-S, Cantley LC . Novel function of phosphatidylinositol 4,5-bisphosphate as a cofactor for brain membrane phospholipase D J Biol Chem 1994 269: 21403–21406

    CAS  Google Scholar 

  29. Tool ATJ, Blom M, Roos D, Verhoeven AJ . Phospholipase D-derived phosphatidic acid is involved in the activation of the CD11b/CD18 integrin in human eosinophils Biochem J 1999 340: 95–101

    Article  CAS  PubMed  Google Scholar 

  30. Erickson RW, Langel-Peveri P, Traynor-Kaplan AE, Heyworth PG, Curnutte JT . Activation of human neutrophil NADPH oxidase by phosphatidic acid or diacylglycerol in a cell-free system J Biol Chem 1999 274: 22243–22250

    Article  CAS  Google Scholar 

  31. Burke JR, Davern LB, Gregor KR, Owczarczak LM . Differentiation of U937 cells enables a phospholipase D-dependent pathway of cytosolic phospholipase A2 activation Biochem Biophys Res Commun 1999 260: 232–239

    Article  CAS  Google Scholar 

  32. Geny B, Stutchfield J, Cockcroft . S. Phorbol ester inhibits polyphosphoinositide phosphodiesterase activity stimulated by either Ca2+, fluoride or GTP analogue in HL-60 membranes and in permeabilised HL-60 cells Cell Signal 1989 1: 165–172

    Article  CAS  Google Scholar 

  33. Geny B, Cost H, Barreau P, Basset M, Le Peuch C, Abita J-P, Cockcroft S . The differentiating agent, retinoic acid, causes an early inhibition of inositol lipid-specific phospholipase C activity in HL-60 cells Cell Signal 1991 3: 11–23

    Article  CAS  Google Scholar 

  34. Grégoire C, Welch H, Astarie-Dequeker C, Maridonneau-Parini I . Expression of azurophil and specific granule proteins during differenciation of NBA cells in neutrophils J Cell Physiol 1998 175: 203–210

    Article  Google Scholar 

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Acknowledgements

This work was supported by Association de Recherche sur le Cancer (ARC) Grant No. 9452. MEM was funded by a fellowship la Fondation pour la Recherche Médicale (FRM) and VM is a fellow from l'Association de Recherche sur la Polyarthrite (ARP). We thank Michel Lanotte for providing NB4 cells and resistant clones, Michael Frohman and David Lambeth for providing hPLD1 and hPLD2 cDNA, respectively, Sylvain Bourgoin for the gift of specific antibodies to PLD1 and PLD2, Muriel Gaudry and Axel Perianin for their help in setting the technique for superoxide ion measurement, Sebastien Bergeot for some technical assistance, Babette Weksler and Jean-Paul Mira for reading the manuscript and stimulating discussions.

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  1. INSERM U332, Laboratoire de Signalisation, Inflammation et Transformation Cellulaire, ICGM, Paris, France

    MEl Marjou, V Montalescot & B Geny

  2. INSERM U445, CHU Cochin-Port-Royal, Paris, France

    A Buzyn

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Marjou, M., Montalescot, V., Buzyn, A. et al. Modifications in phospholipase D activity and isoform expression occur upon maturation and differentiation in vivo and in vitro in human myeloid cells. Leukemia 14, 2118–2127 (2000). https://doi.org/10.1038/sj.leu.2401958

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