In Vivo Efficacy of Recombinant Leukotactin-1 against Cyclophosphamide

  • Lee, Gue-Wha (Mogam Biotechnology Research Institute, Department of Biological Engineering, Inha University) ;
  • Lee, Kong-Ju (Mogam Biotechnology Research Institute) ;
  • Chun, Eun-Young (Mogam Biotechnology Research Institute) ;
  • Lim, In-Whan (Mogam Biotechnology Research Institute) ;
  • Lee, Eun-Kyoung (Mogam Biotechnology Research Institute) ;
  • Park, Mu-Rim (Mogam Biotechnology Research Institute) ;
  • Kim, Dong-Il (Department of Biological Engineering, Inha University) ;
  • Park, Doo-Hong (Mogam Biotechnology Research Institute) ;
  • Yeup Yoon (Mogam Biotechnology Research Institute)
  • 발행 : 2004.01.01

초록

Leukotactin-1 (Lkn-1), a human CC chemokine, has been demonstrated to induce chemotaxis of neutrophils, monocytes, eosinophils and Iym phocytes and has been shown to suppress colony formation of hematopoietic stem and progenitor cells (HSPC) in vitro and in vivo. The temporal suppression of HSPC by chemokines could potentially be applicable for various indications, such as the protection of HSPC from the several anti-proliferating chemotherapeutics in cancer treatments. In order to evaluate the protective effects on myeloid progenitor cells, the recombinant Lkn-1 was produced by Pichia pastoris and tested with cyclophosphamide, cytotoxic chemotherapeutics. The pretreatment of Lkn-1 increased the number of HSPC in bone marrow as well as the potency of resulting progenitor cells after the treatment of cyclophosphamide. Af-ter the first cycle of cyclophosphamide treatment these protections of HSPC correlated with the increased number of white blood cells and neutrophils in the peripheral blood. In lethal conditions created by the repeated administration of cyclophosphamide, the treatment of Lkn-1 enhanced the survival of mice, suggesting the potential use of Lkn-1 as the protective agent for HSPC from various cytotoxic insults.

키워드

참고문헌

  1. Blood v.95 Chemokine receptors and their role in inflammation and inflectious diseases Murdoch,C.;A.Finn
  2. Blood v.90 Chemokines Rollins,B.J.
  3. Immunity v.14 Chemokines, chemokine receptors, and allograft rejection Nelson,P.J.;A.M.Krensky https://doi.org/10.1016/S1074-7613(01)00118-2
  4. Nature v.392 Chemokines and leukocyte traffic Baggiolini,M. https://doi.org/10.1038/33340
  5. New Engl. J. Med. v.338 Chemokines: Chemotaotic cytokines that mediate inflammation Baggiolini,A.D. https://doi.org/10.1056/NEJM199802123380706
  6. Immunol. Rev. v.177 Chemokines, chemokine receotirs and hematopoiesis Youn,B.S.;C.Mantel'H.E.Broxmeyer https://doi.org/10.1034/j.1600-065X.2000.17701.x
  7. Curr. Opin. Rheumatol v.13 Chemokines and angiogenesis Szskanecz,Z.;A.E.Koch https://doi.org/10.1097/00002281-200105000-00009
  8. Nat. Immunol v.2 Chemokines and disease Gerard,C.;B.J.Rollins https://doi.org/10.1038/84209
  9. J. Exp. Med. v.192 Natural protelytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties Detheux,M.;L.Standker;J.Vakili;J.Munch;U.Forssmann;K.Adermann;S.Pohlmann;G.Vassart;F.Kirhhoff;M.Parmentier;W.G.Forssmann https://doi.org/10.1084/jem.192.10.1501
  10. J. Immunol v.159 Molecular cloning of leukotactin-1: A novel human beta-chemokine, a chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist at CC chemokine receotors 1 and 3 Youn,B.S.;S.M.Zhang;E.K.Lee;D.H.Park;H.E.Broxmeyer;P.M.Murphy;M.Locati;J.E.Peast;K.K.Kim;K.Antol;B.S.Kwon
  11. J. Immunol v.162 Differential effects of leukotactin-1 and mactophage inflammatoru protein-1 alpha on neutrophils mediated by CCR1 Zhang,S.;B.S.Youn;J.L.Gao;P.M.Murphy;B.S.Kwon
  12. Exp. Hematol. v.27 Protective effects of BB-10010 treatment on chemotherapy-induced neutropenia in mice Gilmore,G.L.;D.K.DePasquale;R.K.Shadduck https://doi.org/10.1016/S0301-472X(98)00052-6
  13. Nature v.344 Idenrification and characterization of an inhibitor of haemopoietic stem cell proliferation Graham,G.J.;E.G.Wright;R.Hewick;S.D.Wolpe;N.M.Wilkie;D.Donaldson;S.Lorimore;I.B.Pragnell https://doi.org/10.1038/344442a0
  14. Growth Factors v.12 MIP-1 alpha increases the self-renewal capacity of the hemopoietic spleen-colony-forming cells following hydroxyurea treatment in vivo Lord,B.I. https://doi.org/10.3109/08977199509028960
  15. Proc. Natl. Acad. Sci. v.90 Unresponsiveness of promitive chronic myeloid leukemia cells to macropage inflammatory protein 1 alpha, an inhibitor of promitive normal hematopoietic cells Eaves,C.J.;J.D.Cashman;S.D.Wolpe;A.C.Eaves https://doi.org/10.1073/pnas.90.24.12015
  16. Cancer Biology (2nd ed.) King,R.J.B.
  17. J. Hematother. Stem Cell Res. v.12 Effect of leukotactin-1 on the protection in vivo of myeloid progenitor cells against cytoxic chemotherapeutics Kim,W.Y.;H.E.Broxmeyer;I.S.Han;D.H.Park;K.M.Lee;D.S.Vinayl;B.S.Kwon https://doi.org/10.1089/152581603321210181
  18. Stem Cells v.19 Chemokine regulation of notmal and pathologic immune responses Christopherson,K.;R.Hromas https://doi.org/10.1634/stemcells.19-5-388
  19. Br. J. Cancer v.75 Continuous infusion of mactophage inflammatory protein MIP-1 alpha enhances leucocyte recovery and haemopoietic progenitor cell mobilization after cyclophosphamide Marshall,E.;L.B.Woolford;B.I.Lord https://doi.org/10.1038/bjc.1997.294
  20. Atherosclerosis v.161 A nevel chemokine, leukoractin-1, induces chemotaxis, proatherogenic cytokines, and tissue factor expression in atheroslerosis Lee,W.H.;S.H.Kim;E.M.Jeong;Y.H.Choi;D.I.Kim;B.B.Lee;Y.S.Cho;B.S.Kwon.J.E.Park https://doi.org/10.1016/S0021-9150(01)00634-7