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International Journal of Hematology

, Volume 75, Issue 4, pp 401–406 | Cite as

Signal Transduction of Chemokine Platelet Factor 4 in Human Erythroleukemia Cells

  • Yong Jun Liu
  • Shi Hong Lu
  • Zhong Chao Han
Review Article

Abstract

Previous data have demonstrated that CXC-chemokine platelet factor 4 (PF4) inhibits the proliferation of the human erythroleukemia cell line (HEL). However, the mechanism of action is unclear at present. The signaling transduction induced by PF4 in the HEL was compared with that induced by transforming growth factor β1 (TGF-β4), which is also a potent inhibitor of HEL growth. It was found that PF4 had no inhibitory effect on intracellular calcium levels in resting HEL cells. When HEL cells were stimulated with interleukin-3 (IL-3), a rapid increase in the intracellular level of free calcium occurred within 15 to 20 seconds, and this increase was followed by a sustained increase that gradually declined until resting levels were reached 30 to 40 minutes later. PF4 dramatically decreased the transient rise of [Ca2+] and protein kinase C (PKC) activity of HEL cells induced by IL-3. However, PF4 had no inhibitory effect on PKC activation in resting HEL cells. Furthermore, PF4 was found to down-regulate significantly protein tyrosine kinase (PTK) activity. In contrast, TGF-β1 induced an increase in intracellular free calcium concentration and PKC and PTK activity in HEL cells. Furthermore, PF4 significantly increased the messenger RNA (mRNA) level of p21waf1 in HEL cells. These data demonstrate that PF4 acts on HEL cells through a signaling transduction pathway, which is different from that of TGF-β1 and is related to the up-regulatory mRNA level of p21waf1 in HEL cells.

Key words

PF4 TGF-β1 PKC PTK Human erythroleukemia cell line Signaling transduction 

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References

  1. 1.
    Rollins BJ. Chemokines.Blood. 1997;90:909–928.PubMedGoogle Scholar
  2. 2.
    Han ZC, Sensebe L, Abgrall JF, Briere J. Platelet factor 4 inhibits human megakaryocytopoiesis in vitro.Blood. 1990;75:1234–1239.PubMedGoogle Scholar
  3. 3.
    Broxmeyer HE, Sherry B, Cooper S, et al. Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human progenitor cells: interacting effects involving suppression, synergistic suppression, and blocking of suppression.J Immunol. 1993;150:3448–3458.PubMedGoogle Scholar
  4. 4.
    Gewirtz AM, Calabretta B, Rucinski B, et al. Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide.J Clin Invest. 1989; 83: 1477–1482.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kato JY, Matsuoka M, Polyak K, Massague J, Sherr CJ. Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation.Cell. 1994;79:487–496.CrossRefPubMedGoogle Scholar
  6. 6.
    Pagano M, Tam SW, Theodras AM, et al. Role of the ubiquitinproteasome pathway in regulating abundance of the cyclindependent kinase inhibitor p27.Science. 1995;269:682–685.CrossRefPubMedGoogle Scholar
  7. 7.
    Kao JPY, Harootunian AT, Tsien RY. Photochemically generated cytosolic calcium pulses and their detection by fluo-3.J Biol Chem. 1989;264:8179–8184.PubMedGoogle Scholar
  8. 8.
    Yasuda I, Kishimoto A, Tanaka S, Tominaga M, Sakurai A, Nishizuka Y. A synthetic peptide substrate for selective assay of protein kinase C.Biochem Biophys Res Commun. 1990;166: 1220–1227.CrossRefPubMedGoogle Scholar
  9. 9.
    Pike LJ, Gallis B, Casnellie JE, Bornstein P, Krebs EG. Epidermal growth factor stimulates the phosphorylation of synthetic tyrosinecontaining peptides by A431 cell membranes.Proc Natl Acad Sci US A. 1982;79:1443–1447.CrossRefGoogle Scholar
  10. 10.
    Umezawa K, Hori T, Tajima H, Imoto M, Isshiki K, Takeuchi T. Inhibition of epidermal growth factor-induced DNA synthesis by tyrosine kinase inhibitors.FEBS Lett. 1990;260:198–200.CrossRefPubMedGoogle Scholar
  11. 11.
    Sambrook J, Fritsch EF, Maniatis T.Molecular Cloning: A Laboratory Manual. Vol. 1-3. Plainview, NY: Cold Spring Harbor Laboratory Press; 1989.Google Scholar
  12. 12.
    Newton AC. Protein kinase C: structure, function, and regulation.J Biol Chem. 1995;270:28495–28498.CrossRefPubMedGoogle Scholar
  13. 13.
    Foreback JL, Sarma V, Yeager NR, Younkin EM, Remick DG, Ward PA. Blood mononuclear cell production of TNF-α and IL-8: engagement of different signal transduction pathways including the p42 MAP kinase pathway.J Leukoc Biol. 1998;64:124–133.CrossRefPubMedGoogle Scholar
  14. 14.
    Maxfield FR. Ca2+ regulation of neutrophil chemotaxis.Trends Cell Biol. 1993;3:386–391.CrossRefPubMedGoogle Scholar
  15. 15.
    Thelen M, Dewald B, Baggiolini M. Neutrophil signal transduction and activation of the respiratory burst.Physiol Rev. 1993;73: 797–822.CrossRefPubMedGoogle Scholar
  16. 16.
    Isfort RJ, Ihle JN. Multiple hematopoietic growth factors signal through tyrosine phosphorylation.Growth Factors. 1990;2:213–220.CrossRefPubMedGoogle Scholar
  17. 17.
    Ullich A, Schlessingeer J. Signal transduction by receptors with tyrosine kinase activity.Cell. 1990;61:203–212.CrossRefGoogle Scholar
  18. 18.
    Han ZC, Bellucci S, Wan HY, Caen JP. New insights into the regulation of megakaryocytopoiesis by haematopoietic and fibroblast growth factors and transforming growth factor β.Br J Haematol. 1992;81:1–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Han ZC, Maurer AM, Bellucci S, et al. Inhibitory effect of platelet factor 4 (PF4) on the growth of human erythroleukemia cells: proposed mechanism of action of PF4.J Lab Clin Med. 1992;120: 645–660.PubMedGoogle Scholar
  20. 20.
    Xi XD, Caen JP, Fournier S, et al. Direct and reversible inhibition of platelet factor 4 on megakaryocyte development from CD34+ cord blood cells: comparative studies with transforming growth factor β1.Br J Haematol. 1996;93:490.CrossRefGoogle Scholar
  21. 21.
    Hu X, Zuckerman KS. Transforming growth factor: signal transduction pathways, cell cycle mediation, and effects on hematopoiesis.J Hematother Stem Cell Res. 2001;10:67–74.CrossRefPubMedGoogle Scholar
  22. 22.
    Mui ALF, Wakao H, Harada N, O’Farrell AM, Migajjma A. Interleukin-3, granulocyte-macrophage colony-stimulating factor, and interleukin-5 transduce signals through two forms and STAT5.J Leukoc Biol. 1995;57:799–803.CrossRefPubMedGoogle Scholar
  23. 23.
    Whelham MJ, Duronio V, Sanghera JS, Pelech SL, Schrader JW. Multiple hematopoietic growth factors stimulate activation of mitogen-activated protein kinase family member.J Immunol. 1992; 149:1683–1693.Google Scholar
  24. 24.
    Gupta SK, Singh JP. Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression.J Cell Biol. 1994;127:1121–2711.CrossRefPubMedGoogle Scholar
  25. 25.
    Gentilini G, Kirschbaum NE, Augustine JA, Aster RH, Visendtin GP. Inhibition of human umbilical vein endothelial cell proliferation by the CXC chemokine, platelet factor 4 (PF4), is associated with impaired downregulation of p21cip1/WAF1.Blood. 1999;939: 25–33.Google Scholar
  26. 26.
    Resnitzky D, Hengst L, Reed SI. Cyclin A—associated kinase activity is rate limiting for entrance into S phase and is negatively regulated in G1 by p27Kip1.Mol Cell Biol. 1995;15:4347–4352.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression.Genes Dev. 1999;13:1501–1512.CrossRefPubMedGoogle Scholar
  28. 28.
    Pavletich NP. Mechanisms of cyclin-dependent kinase regulation: structure of Cdks, their cyclin activators, and Cip and INK4 inhibitors.J Mol Biol. 1999;287:821–828.CrossRefPubMedGoogle Scholar
  29. 29.
    Dyson N. The regulation of E2F by pRB-family proteins.Genes Dev. 1998;12:2245–2262.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  1. 1.National Laboratory of Experimental Hematology, Institute of HematologyChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinPeople’s Republic of China

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