Molecular Biology Reports

, Volume 37, Issue 5, pp 2149–2156 | Cite as

Leukotactin-1/CCL15 induces cell migration and differentiation of human eosinophilic leukemia EoL-1 cells through PKCδ activation

Article

Abstract

Leukotactin-1 (Lkn-1)/CCL15 is a CC chemokine that binds to the CCR1 and CCR3. Lkn-1 functions as an essential factor in the migration of monocytes, lymphocytes, and neutrophils. Although eosinophils express both receptors, the role of Lkn-1 in immature eosinophils remains to be elucidated. In this present study, we investigated the contribution of the CCR1-binding chemokines to chemotactic activity and in the differentiation in the human eosinophilic leukemia cell line EoL-1. Lkn-1 induced the stronger migration of EoL-1 cells than other CCR1-binding chemokines such as RANTES/CCL5, MIP-1α/CCL3 and HCC-4/CCL16. Lkn-1-induced chemotaxis was inhibited by pertussis toxin, an inhibitor of Gi/Go protein; U73122, an inhibitor of phospholipase C and rottlerin, an inhibitor of protein kinase C delta (PKCδ). Lkn-1 increased PKCδ activity, which was partially blocked by the pertussis toxin and U73122. Lkn-1 enhanced the butyric acid-induced differentiation via PKCδ after binding to the increased CCR1 because Lkn-1 caused EoL-1 cells to change morphologically into mature eosinophil-like cells. Likewise, Lkn-1 increased the expression of both eosinophil peroxidase (EPO) and the major basic protein (MBP). PKCδ activation due to Lkn-1 is involved in migration, as well as the butyric acid-induced differentiation. This finding contributes to an understanding of CC chemokines in eosinophil biology and to the development of novel therapies for the treatment of eosinophilic disorders. This study suggests the pivotal roles of Lkn-1 in the regulation of the movement and development of eosinophils.

Keywords

Leukotactin-1 Eosinophils Cell migration Differentiation Protein kinase C δ 

Abbreviations

Lkn-1

Leukotactin-1

PKCδ

Protein kinase C δ

EPO

Eosinophil peroxidase

MBP

Major basic protein

References

  1. 1.
    Baggiolini M, Dewald B, Moser B (1997) Human chemokines: an update. Annu Rev Immunol 15:675–705CrossRefPubMedGoogle Scholar
  2. 2.
    Rollins BJ (1997) Chemokines. Blood 90:909–928PubMedGoogle Scholar
  3. 3.
    Youn BS, Zhang SM, Lee EK, Park DH, Broxmeyer HE, Murphy PM et al (1997) Molecular cloning of leukotactin-1: a novel human beta-chemokine, a chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist at CC chemokine receptors 1 and 3. J Immunol 159:5201–5205PubMedGoogle Scholar
  4. 4.
    Yu R, Kim CS, Kawada T, Kwon TW, Lim TH, Kim YW et al (2004) Involvement of leukotactin-1, a novel CC chemokine, in human atherosclerosis. Atherosclerosis 174:35–42CrossRefPubMedGoogle Scholar
  5. 5.
    Jang SW, Kim YS, Lee YH, Ko J (2007) Role of human LZIP in differential activation of the NF-kappaB pathway that is induced by CCR1-dependent chemokines. J Cell Physiol 211:630–637CrossRefPubMedGoogle Scholar
  6. 6.
    Pardigol A, Forssmann U, Zucht HD, Loetscher P, Schulz-Knappe P, Baggiolini M et al (1998) HCC-2, a human chemokine: gene structure, expression pattern, and biological activity. Proc Natl Acad Sci USA 95:6308–6313CrossRefPubMedGoogle Scholar
  7. 7.
    Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z, Kowalska MA et al (2001) Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 97:3075–3085CrossRefPubMedGoogle Scholar
  8. 8.
    Broxmeyer HE (2001) Regulation of hematopoiesis by chemokine family members. Int J Hematol 74:9–17CrossRefPubMedGoogle Scholar
  9. 9.
    Han IS, Ra JS, Kim MW, Lee EA, Jun HY, Park SK et al (2003) Differentiation of CD34 + cells from human cord blood and murine bone marrow is suppressed by C6 beta-chemokines. Mol Cells 15:176–180PubMedGoogle Scholar
  10. 10.
    Kim WY, Broxmeyer HE, Han IS, Park DH, Lee KM, Vinay DS et al (2003) Effect of leukotactin-1 on the protection in vivo of myeloid progenitor cells against cytotoxic chemotherapeutics. J Hematother Stem Cell Res 12:107–113CrossRefPubMedGoogle Scholar
  11. 11.
    Ko J, Kim IS, Jang SW, Lee YH, Shin SY, Min DS et al (2002) Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells. FEBS Lett 515:159–164CrossRefPubMedGoogle Scholar
  12. 12.
    Wong CK, Ho CY, Lam SW, Zhang JP, Hjelm NM (1999) Differentiation of a human eosinophilic leukemic cell line, EoL-1: characterization by the expression of cytokine receptors, adhesion molecules, CD95 and eosinophilic cationic protein (ECP). Immunol Lett 68:317–323CrossRefPubMedGoogle Scholar
  13. 13.
    Bankers-Fulbright JL, Kita H, Gleich GJ, O’Grady SM (2001) Regulation of human eosinophil NADPH oxidase activity: a central role for PKC delta. J Cell Physiol 189:306–315CrossRefPubMedGoogle Scholar
  14. 14.
    Sano M, Leff AR, Myou S, Boetticher E, Meliton AY, Learoyd J et al (2005) Regulation of interleukin-5-induced beta2-integrin adhesion of human eosinophils by phosphoinositide 3-kinase. Am J Respir Cell Mol Biol 33:65–70CrossRefPubMedGoogle Scholar
  15. 15.
    Kim IS, Ryang YS, Kim YS, Jang SW, Sung HJ, Lee YH et al (2003) Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKC delta/Ras cascades in HOS cells. Life Sci 73:447–459CrossRefPubMedGoogle Scholar
  16. 16.
    Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242CrossRefPubMedGoogle Scholar
  17. 17.
    Ishihara K, Takahashi A, Kaneko M, Sugeno H, Hirasawa N, Hong J et al (2007) Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors. Life Sci 80:1213–1220CrossRefPubMedGoogle Scholar
  18. 18.
    Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J et al (2003) A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348:1201–1214CrossRefPubMedGoogle Scholar
  19. 19.
    Cools J, Quentmeier H, Huntly BJ, Marynen P, Griffin JD, Drexler HG et al (2004) The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood 103:2802–2805CrossRefPubMedGoogle Scholar
  20. 20.
    Pan J, Quintás-Cardama A, Manshouri T, Giles FJ, Lamb P, Tefferi A et al (2007) The novel tyrosine kinase inhibitor EXEL-0862 induces apoptosis in human FIP1L1-PDGFR-alpha-expressing cells through caspase-3-mediated cleavage of Mcl-1. Leukemia 21:1395–1404CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Department of Biology, College of Natural SciencesDaejeon UniversityDaejeonRepublic of Korea
  2. 2.Department of Biomedical Laboratory Science, School of MedicineEulji UniversityDaejeonRepublic of Korea

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