Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Expression of Stromal Derived Factor-1 is Upregulated In Macrophages during Thymic Regeneration in Adult Rat

흰쥐 가슴샘 재생과정 동안 대식세포에서 SDF-1의 발현증가

  • Park, Hyun-Joo (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Kim, Jong-Gab (Department of Physiology, Pusan National University) ;
  • Yoon, Sik (Department of Anatomy, School of Medicine, Pusan National University) ;
  • Bae, Moon-Kyoung (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Bae, Soo-Kyung (Department of Physiology, Pusan National University)
  • 박현주 (부산대학교 치의학전문대학원 구강생리학교실) ;
  • 김종갑 (부산대학교 의학전문대학원 생리학교실) ;
  • 윤식 (부산대학교 의학전문대학원 해부학교실) ;
  • 배문경 (부산대학교 치의학전문대학원 구강생리학교실) ;
  • 배수경 (부산대학교 의학전문대학원 생리학교실)
  • Published : 2009.08.30
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Abstract

Stromal derived factor-1 (SDF-1 or CXCL12), one of the CXC chemokines, is widely expressed in many tissues, including the thymus. The thymus can regenerate to its normal mass within 14 days after acute involution induced by cyclophosphamide (CY) in adult rats. Despite the established role of SDF-1 signaling in the development of T and B lymphocytes in the thymus, it has not yet been associated with the regeneration of the adult thymus. The purpose of this study was to investigate whether SDF-1, which is expressed in thymic stromal cells, is modulated during thymic regeneration in adult rats. Here, we showed that SDF-1 mRNAs were expressed in high levels in the thymocyte and thymic stromal cells at day 7 of the CY model. SDF-1 protein was shown to be present at the cortex-medulla junction, paraseptum and within the thymic medulla. Double-immunofluorescence for SDF-1 and ED-1 showed that strong SDF-1 expression was detected in the macrophages of the medulla region displaying immunoreactivity for ED-1 during thymus regeneration. Taken together, our results demonstrated that SDF-1 expression increased in regenerating thymic macrophages, suggesting the roles of SDF-1 as a chemo-attractant for damaged cells produced in the process of thymic regeneration after acute involution induced by CY.

성체흰쥐의 경우 항암제인 싸이클로포스파마이드(CY)처리로 퇴축된 가슴샘은 2주 후에 정상조직으로 재생된다. 가슴샘 발생과정에서 이미 알려진 SDF-1 신호전달의 중요성과는 달리 성체의 가슴샘 재생과정에서 그 역할에 관해서는 알려진 바 전혀 없다. 본 연구의 목적은 발생중인 가슴샘에서 발현이 증가된다고 이미 알려져 있는 SDF-1이 성체의 가슴샘재생과정에서 어떤 발현 양상을 보이는지를 조사하는 것이다. 본 연구에서는 사이클로포스파마이(cyclophosphamide: CY)를 투여하여 가슴샘의 급성 퇴축을 유발시킨 후, 가슴샘 재생과정동안 SDF-1의 발현 특성을 면역조직화학, 이중면역염색 형광법, 역전사 중합효소 연쇄반응법을 이용하여 조사하였다. 그 결과, SDF-1은 가슴샘의 급성 퇴축 이후 7일째 되는 시기에 mRNA와 단백질의 양이 급격히 증가하였으며, 이중면역염색 형광법을 통해 큰포식 세포와 위치적 분포가 일치함을 확인하였다. 따라서, 본 연구 결과들을 통해 SDF-1은 가슴샘의 급성 퇴축 초기 과정에서 나타나는 손상된 세포를 처리하는 큰포식 세포의 기능 조절에 관여할 것으로 생각된다.

Keywords

References

  1. Anderson, G., N. C. Moore, J. J. Owen, and E. J. Jenkinson. 1996. Cellular interactions in thymocyte development. Annu. Rev. Immunol. 14, 73-99 https://doi.org/10.1146/annurev.immunol.14.1.73
  2. Andreas, S. 2008. Chemokines in vascular dysfunction and remodeling. Arterioscler Thromb. Vasc. Biol. 28, 1950-1959 https://doi.org/10.1161/ATVBAHA.107.161224
  3. Campbell, J. J., J. Pan, and E. C. Butcher. 1999. Cutting edge: developmental switches in chemokine responses during T cell maturation. J. Immunol. 163, 2353-2357 https://doi.org/10.1172/JCI8511
  4. Faas, S. F., J. L. Rothsteiin, B. L. Kreider, G. Rovera, and B. B. Knowles. 1993. Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. Eur. J. Immunol. 23, 1201-1214 https://doi.org/10.1002/eji.1830230602
  5. Kim, C. H., L. M. Pelus, J. R. White, and H. E. Broxmeyer. 1998. Differential chemotactic behavior of developing T cells in response to thymic chemokines. Blood 91, 4434-4443
  6. Klein, R. S. and J. B. Rubin. 2004. Immune and nervous system CXCL12 and CXCR4: parallel roles in patterning and plasticity. Trends Immunol. 25, 306-314 https://doi.org/10.1016/j.it.2004.04.002
  7. Kucia, M., K. Jankowski, R. Reca, M. Wysoczynski, L. Bandura, D. J. Allendorf, J. Zhang, J. Ratajczak, and M. Z. Ratajczak. 2004. CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J. Mol. Histol. 35, 233-245 https://doi.org/10.1023/B:HIJO.0000032355.66152.b8
  8. Luster, A. D. 1998. Chemokines-chemotactic cytokines that mediate inflammation. New England Journal of Medicine 338, 436-445 https://doi.org/10.1056/NEJM199802123380706
  9. Milicevic, N. M., Z. Milicevic, O. Piletic, S. Mujovic, and V. Ninkov. 1984. Patterns of thymic regeneration in rats after single or divided doses of cyclophosphamide. J. Comp. Pathol. 94, 197-202 https://doi.org/10.1016/0021-9975(84)90040-9
  10. Miller, J. P. 1961. Immunological function of the thymus. Lancet. 2, 748-749
  11. Nagasawa, T., H. Kikutani, and T. Kishimoto. 1994. Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc. Natl. Acad. Sci. 91, 2305-2309 https://doi.org/10.1073/pnas.91.6.2305
  12. Park, H. J., M. N. Kim, J. G. Kim, Y. H. Bae, M. K. Bae, H. J. Wee, T. W. Kim, B. S. Kim, J. B. Kim, S. K. Bae, and S. Yoon. 2007. Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat. BBA - Molecular Cell Research. 1773, 1462-1472 https://doi.org/10.1016/j.bbrc.2007
  13. Ratajczak, M. Z., E. Zuba-Surma, M. Kucia, R. Reca, W. Wojakowski, and J. Ratajczak. 2006. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia 20, 1915-1924 https://doi.org/10.1038/sj.leu.2404357
  14. Ritter, M. A. and D. B. Palmer. 1999. The human thymic microenvironment: new approaches to functional analysis. Semin Immunol. 11, 13-21 https://doi.org/10.1006/smim.1998.0148
  15. Sakihama, H., T. Masunaga, K., T. Hashimoto, M. Inobe, S. Todo, and T. Uede. 2004. Stromal cell-derived factor-1 and CXCR4 interaction is critical for development of transplant arteriosclerosis. Circulation 110, 2924-2930 https://doi.org/10.1161/01.CIR.0000146890.93172.6C
  16. Shanker, A. 2004. Is thymus redundant after adulthood? Immunol. Lett. 91, 79-86 https://doi.org/10.1016/j.imlet.2003.12.012
  17. Taub, D. D. and D. L. Longo. 2005. Insights into thymic aging and regeneration. Immunol. Rev. 205, 72-93 https://doi.org/10.1111/j.0105-2896.2005.00275.x
  18. Wald, O., O. Pappo, R. Safadi, M. Dagan-Berger, K. Beider, H. Wald, S. Franitza, I. Weiss, S. Avniel, P. Boaz, J. Hanna, G. Zamir, A. Eid, O. Mandelboim, U. Spengler, E. Galun, and A. Peled. 2004. Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus. Eur. J. Immunol. 34, 1164-1174 https://doi.org/10.1002/eji.200324441
  19. Yoon, S., Y. H. Yoo, B. S. Kim, and J. J. Kim. 1997. Ultrastructural alterations of the cortical epithelial cells of the rat thymus after cyclophosphamide treatment. Histol. Histopathol. 12, 401-413
  20. Zaitseva, M., T. Kawamura, R. Loomis, H. Goldstein, A. Blauvelt, and H. Golding. 2002. Stromal-derived factor 1 expression in the human thymus. J. Immunol. 15, 2609-2617