Journal of Animal Science and Technology

Korean Society of Animal Sciences and Technology (한국축산학회)
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Immunohistochemical Study on the TNFα-Secreting Macrophages and Endothelial Cells in the Porcine Corpus Luteum

돼지 황체에서 TNFα-분비 대식세포와 내피세포에 관한 면역조직화학적 연구

  • Park, C.S. (Division of Animal Science & Resources, Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Han, S.R. (College of Medicine, Chungnam National University) ;
  • Kim, S.I. (College of Medicine, Chungnam National University) ;
  • Cho, K.J. (College of Visual Images and Health, Kongju National University) ;
  • Kim, W.S. (College of Medicine, Chungnam National University)
  • Published : 2005.10.31
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Abstract

In the corpus luteum, TNF$\alpha$ is known to induce functional and structural luteolysis. In addition, it acts as luteotropic agent during the initial and early stage of luteal development. In spite of its importance in corpus luteal development, there is still different opinions for the source cells of TNF$\alpha$ in the corpus luteum. One is the macrophages only, and the other is macrophages are the main source and endothelial cells are the minor source. In this experiment, using the porcine corpora lutea of pregnancy and ovulatory stages, hematoxylin-eosin stain, macrophage and TNF$\alpha$ immunohistochemistry were carried to reveal the sources of TNF$\alpha$. As a result, MAC 387-positive macrophages were present in all the stages of corpora lutea. In the mature corpora lutea of nonpregnant stages, the sites of MAC 387-positive macrophages and those of TNF$\alpha$- positive macrophages were coincided, and the sites of endothelial cells and those of TNF$\alpha$-positive endothelial cells were nearly coincided. But, in the mature CL of pregnant stage, mid- and advanced luteolytic stages of both nonpregnant and pregnant stages, the sites of MAC 387-positive macrophages and those of TNF$\alpha$-positive macrophages were coincided, but not in the endothelial cells. Accordingly, it can be concluded that macrophages are the main source of TNF$\alpha$ in the corpus luteum and endothelial cells are the minor source in the mature and mid-lytic stages, but, in the advanced luteolytic stage, macrophages are the only source of TNF$\alpha$.

황체내 TNF$\alpha$는 큰황체세포를 포함한 황체내 세포들의 사망을 일으키고, 황체내 혈관의 퇴화와 프로게스테론 농도의 감소를 초래하는 등 황체의 구조적 및 기능적 퇴화를 유발하는 것으로 밝혀졌다. 반면 이와는 대조적으로 TNF$\alpha$는 황체발달의 초기에는 황체자극효과를 가지고 있다는 보고도 있다. 황체내에서 TNF$\alpha$의 중요성에도 불구하고, 아직 이 물질의 분비원이 대식세포라는 보고들과 대식세포는 주된 분비원이고 내피세포에서도 소량 분비된다는 보고 등 이견이 있다. 이를 알아보기 위해 저자들은 돼지에서 비임신기와 임신기의 성숙황체와 용해황체를 이용하여 대식세포와 TNF$\alpha$ 면역조직화학을 실시한 결과, 성숙황체내에서 TNF$\alpha$의 주된 분비원은 대식세포이고 내피세포도 일부 분비하는 것을 확인하였으며, 황체용해가 진행되면서 내피세포가 TNF$\alpha$의 분비와 반응에 다양성과 역동성을 보이고 있음을 추정할 수 있었다.

Keywords

References

  1. Abdo, M. A. and Dharmarajan, A. M. 1997. Role of tumor necrosis factor-alpha in corpus luteum regression. In: Proceedings of the 8th Annual Combined Biological Sciences Meeting, Abstract 16, Perth
  2. Adashi, E. Y., Resnick, C. E., Packman, J. N., Hurwitz, A. and Payne D. W. 1990. Cytokine- mediated regulation of ovarian function: tumor necrosis factor ${\alpha}$ inhibits gonadotropin-supported progesterone accumulation by differentiating and luteinized murine granulosa cells. Am. J. Obstet. Gynecol. 162:889-899 https://doi.org/10.1016/0002-9378(90)91289-O
  3. Asselin, E., Xiao, C. W., Wang, Y. F. and Tsang, B. K. 2000. Mammalian follicular development and atresia: role of apoptosis. Biol. Signals Recept. 9:87-95 https://doi.org/10.1159/000014627
  4. Bacci, M. L., Barazzoni, A. M., Forni, M., Costerbosa, A. L., Youngquist, R. S. and Smith, M. F. 1996. In situ detection of apoptosis in regressing corpus luteum of pregnant sow: evidence of an early presence of DNA fragmentation. Domest. Anim. Endocrinol. 13:361-372 https://doi.org/10.1016/0739-7240(96)00049-5
  5. Bagavandoss, P., Kunkel, S. L., Wiggins, R. C. and Keyes, P. L. 1988. Tumor necrosis factor-${\alpha}$ production and localization of macrophages and T lymphocytes in the rabbit corpus luteum. Endocrinology 122:1185-1187 https://doi.org/10.1210/endo-122-3-1185
  6. Bagavandoss, P., Wiggins, R. C., Kunkel, S. L., Remick, D. G. and Keyes, P. L. 1990. Tumor necrosis factor production and accumulation of inflammatory cells in the corpus luteum of pseudopregnancy and pregnancy in rabbits. Biol. Reprod. 42:367-376 https://doi.org/10.1095/biolreprod42.2.367
  7. Bagavandoss, P. and Wilks, J. W. 1991. Isolation and chaaracterization of microvascular endothelial cells from developing corpus luteum. Biol. Reprod. 44:1132-1139 https://doi.org/10.1095/biolreprod44.6.1132
  8. Benyo, D. F. and Pate, J. L. 1992. Tumor necrosis factor-alpha alters bovine luteal cell synthetic capacity and viability. Endocrinology 130:854-860 https://doi.org/10.1210/en.130.2.854
  9. Beutler, B. and Cerami, A. 1988. Cachectin (tumor necrosis factor) : a macrophage hormone governing cellular metabolism and inflammatory response. Endocr. Rev. 9:57-66 https://doi.org/10.1210/edrv-9-1-57
  10. Beutler, B. and Cerami, A. 1989. The biology of cachectin/TNF${\alpha}$ - a primary mediator of the host response. Annu. Rev. Immunol. 7:625-655 https://doi.org/10.1146/annurev.iy.07.040189.003205
  11. Beutler, B. and van Huffel, C. 1994. Unraveling function in the $TNF{\alpha}$ ligand and receptor families. Science 264:667-668 https://doi.org/10.1126/science.8171316
  12. Brannstrom, M. B. and Norman, R. J. 1993. Invelvement of leukocytes and cytokines in the ovulatory process and corpus luteum function. Hum. Reprod. 8:1762-1775
  13. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N. and Williamson, B. 1975. An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. USA 72:3666-3670 https://doi.org/10.1073/pnas.72.9.3666
  14. Chen, H., Marcinkiewicz, J. L., Sancho-Tello, M., Hunt, J. S. and Terranova, P. F. 1993. Tumor necrosis factor-${\alpha}$ gene expression in mouse oocytes and follicular cells. Biol. Reprod. 48: 707-714 https://doi.org/10.1095/biolreprod48.4.707
  15. Chen, Y., Feng, Q. and Liu, Y. 1999. Expression of the steroidogenic acute regulatory protein and luteinizing hormone receptor and their regulation by tumor necrosis factor-${\alpha}$ in rat corpora lutea. Biol. Reprod. 60:419-427 https://doi.org/10.1095/biolreprod60.2.419
  16. Davis, J. S., Rueda, B. R. and Spanel-Borowski, K. 2003. Microvascular endothelial cells of the corpus luteum. Reprod. Biol. Endocrinol. 1:89-104 https://doi.org/10.1186/1477-7827-1-89
  17. Hehnke-Vagnoni, K. E., Clark, C. L., Taylor, M. J. and Ford, S.P. 1995. Presence and localization of tumor necrosis factor ${\alpha}$in the corpus luteum of nonpregnant and pregnant pigs. Biol. Reprod. 53:1339-1344 https://doi.org/10.1095/biolreprod53.6.1339
  18. Jo, T., Tomiyama, T., Ohashi, K., Saji, F., Ozaki, M., Yamamoto, R., Yamamoto, T., Nishizawa, Y. and Terada, N. 1995. Apoptosis of cultured mouse luteal cells induced by tumor necrosis factor-${\alpha}$ and interferon-${\gamma}$. Anat. Rec. 241:70-76 https://doi.org/10.1002/ar.1092410110
  19. Juengel, J. L., Garverick, H. A., Johnson, A. L., Youngquist, R. S. and Smith, M. F. 1993. Apoptosis during lutela regression in cattle. Endocrinology 132:249-254 https://doi.org/10.1210/en.132.1.249
  20. Kaipia, A. and Hsueh, A. J. 1997. Regulation of ovarian follicle atresia. Annu. Rev. Physiol. 59: 349-363 https://doi.org/10.1146/annurev.physiol.59.1.349
  21. Komatsu, K., Manabe, N., Kiso, M., Shimabe, M. and Miyamoto, H. 2003. Changes in localization of immune cells and cytokines in corpora lutea during luteolysis in murine ovaries. J. Exp. Zoology 296A;152-159 https://doi.org/10.1002/jez.a.10246
  22. Kondo, H., Maruo, T. and Mochizuki, M. 1995. Immunohistochemical evidence for the presence of tumor necrosis factor-${\alpha}$ in the infant and adult human ovary. Endocr. J. 42:771-780 https://doi.org/10.1507/endocrj.42.771
  23. Marcinkiewicz, J. L., Krishna, A., Cheung, C. M. and Terranova, P. F. 1994. Oocytic tumor necrosis factor alpha: localization in the neonatal rat ovary and throughout follicular development in the adult rat. Biol. Reprod. 50:1251-1260 https://doi.org/10.1095/biolreprod50.6.1251
  24. Maylor, M. S., Stamp, G. W. H., Foulkes, W. D., Eccles, D. and Balkwill, F. R. 1993. Tumor necrosis factor and its receptors in human ovarian cancer. J. Clin. Invest. 91:2194-2206 https://doi.org/10.1172/JCI116446
  25. Miyamoto, Y., Sakumoto, R., Sakabe, Y., Miyake, M., Okano, A. and Okuda, K. 2002. Tumor necrosis factor-${\alpha}$ receptors are present in the corpus luteum throughout the estrous cycle and during the early gestation period in pigs. Reprod. Domest. Anim. 37:105-110 https://doi.org/10.1046/j.1439-0531.2002.00324.x
  26. Murdoch, W. J., Colgin, D. C. and Ellis, J. A. 1997. Role of tumor necrosis factor-${\alpha}$ in the ovulatory mechanism of ewes. J. Anim. Sci. 75: 1601-1605
  27. Nariai, K., Kanayama, K., Endo, T. and Tsukise, A. 1995. Effects of TNF${\alpha}$ injection into the ovarian parenchyma on luteal blood vessels in rabbits. Endocr. J. 42:761-766 https://doi.org/10.1507/endocrj.42.761
  28. Niedbala, M. J. 1993. Cytokine regulation or endothelial cell extracellular proteolysis. In Cheronis JC, Repine JE(eds.), Proteases, Proteases Inhibitors and Protease-Derived Peptides. Boston: Birkhauser Verlag; pp. 179-193
  29. Niswender, G. D., Juengel, J. L., Silva, P. J., Rollyson, M. K. and McIntush, E. W. 2000. Mechanism controlling the function and life span of the corpus luteum. Physiological Reviews 80(1):1-29
  30. Niswender, G. D. and Nett, T. M. 1988. The corpus luteum and its control. In: The Physiology of Reproduction, E. Knobil and JD Neil(ed.), Raven Press, New York, p. 489-525
  31. Pate, J. L. 1995. Involvement of immune cells in regulation of ovarian function. J. Reprod. Fertil. 49(Suppl):365-377
  32. Pitzel, L., Jarry, H. and Wuttke, W. 1993. Effects and interaction of prostaglandin F2 alpha, oxytocin, and cytokines on steroidogenesis of porcine luteal cells. Endocrinology 132:751-756 https://doi.org/10.1210/en.132.2.751
  33. Richards, R. G. and Almond, G. W. 1994. Identification and distribution of tumor necrosis factor alpha receptor in pig corpora lutea. Biol. Reprod. 51:1285-1291 https://doi.org/10.1095/biolreprod51.6.1285
  34. Roby, K. F. and Terranova, P. F. 1989. Localization of tumor necrosis factor(TNF${\alpha}$) in the rat and bovine ovary using immunohistochemistry and cell blot: evidence for granulosa production. In: Hirshfield AN(ed.), Growth Factors and the Ovary. New York, Plenum Publishing Corporation, pp. 273-278
  35. Roby, K. F. and Terranova, P. F. 1990. Effects of tumor necrosis factor-alpha in vitro on steroido- genesis of healthy and atretic follicles of the rat: theca as a target. Endocrinology 126:2711-2718
  36. Roby, K. F., Weed, J., Lyles, R. and Terranova, P. F. 1990. Immunological evidence for a human ovarian tumor necrosis factor-${\alpha}$. J. Clin. Endocrinol. Metab. 71:1096-1102 https://doi.org/10.1210/jcem-71-5-1096
  37. Rueda, B. R., Wegner, J. A., Marion, S. L., Wahlen, D. D. and Hoyer, P. B. 1995. Internu- cleosomal DNA fragmentation in ovine luteal tissue associated with luteolysis: in vivo and in vitro analysis. Biol. Reprod. 52:305-312 https://doi.org/10.1095/biolreprod52.2.305
  38. Sakumoto, R., Berisha, B., Kawate, N., Schams, D. and Okuda, K. 2000. Tumor necrosis factor-${\alpha}$ and its receptor in bovine corpus luteum throughout the estrous cycle. Biol. Reprod. 62:192-199 https://doi.org/10.1095/biolreprod62.1.192
  39. Sakumoto, R. and Okuda, K. 2004. Possible actions of TNF${\alpha}$ in ovarian function. J. Reprod. Dev. 50:39-46 https://doi.org/10.1262/jrd.50.39
  40. Sakumoto, R., Shibaya, M. and Okuda, K. 2003. Tumor necrosis factor-${\alpha}$ inhibits progesterone and estradiol-17${\beta}$ production from cultured granulosa cells: Presence of TNF${\alpha}$receptors in bovine granulosa and theca cells. J. Reprod. Dev. 49: 441-449 https://doi.org/10.1262/jrd.49.441
  41. Schams, D., Schmidt, K. and Schlegel, W. 1995. Effects of growth factors on prostaglandin secretion of bovine luteal cells in vitro at different stages of the luteal phase. Biol. Reprod. 52(Supple 1):569
  42. Shakil, T. and Whitehead, S. A. 1994. Inhibitory action of peritoneal macrophages on progesterone secretion from co-cultured rat granulosa cells. Biol. Reprod. 50:1183-1189 https://doi.org/10.1095/biolreprod50.5.1183
  43. Spanel-Borowski, K., Ricken, A. M., Kress, A. and Huber, P. R. 1994. Isolation of granulosa-like cells from the bovine secretory corpus luteum and their characterization in long-term culture. Anat. Rec. 239:269-279 https://doi.org/10.1002/ar.1092390305
  44. Tartaglia, L. A. and Goeddel, D. V. 1992. Two TNF${\alpha}$ receptors. Immunol. Today 13:151-153 https://doi.org/10.1016/0167-5699(92)90116-O
  45. Terranova, P. F. 1997. Potential roles of tumor necrosis factor-${\alpha}$ in follicular development, ovulation and the life span of the corpus luteum. Domest. Animal Endocrinol. 14:1-15 https://doi.org/10.1016/S0739-7240(96)00094-X
  46. Townson, D. H., O'Connor, C. L. and Pru, J. K. 2002. Expression of MCP-1 and distribution of immune cell populations in the bovine corpus luteum throughout the estrous cycle. Biol. Reprod. 66:361-366 https://doi.org/10.1095/biolreprod66.2.361
  47. Vaskivuo, T. E., Ottander, U., Oduwole, O., Isomaa, V., Vihko, P., Olofsson, J. I. and Tapanainen, J. S. 2002. Role of apoptosis, apoptosis- related factors and 17-${\beta}$ hydroxysteroid dehydro- genases in human corpus luteum regression. Mol. Cell Endocrinol. 194:191-200 https://doi.org/10.1016/S0303-7207(02)00087-4
  48. Vassalli, P. 1992. The pathophysiology of tumor necrosis factors. Annu. Rev. Immunol. 10:411-452 https://doi.org/10.1146/annurev.iy.10.040192.002211
  49. Wang, L. J., Brannstrom, M., Robertson, S. A. and Norman, R. J. 1992. Tumor necrosis factor ${\alpha}$ in the human ovary: presence in follicular fluid and effects on cell proliferation and prostaglandin production. Fertil. Steril. 58:934-940
  50. Wuttke, W., Jarry, H., Pitzel, L., Knoke, I., Cieslar, S. and Dietrich, E. 1992. Luteotrophic and luteolytic effects of peptides in the porcine and human corpus luteum. In : Proceedings of the IXth Ovarian Workshop; Chapel Hill, NC, Abstract 16
  51. Wuttke, W., Jarry, H., Pitzel, L., Knoke, I. and Spiess, S. 1993. Luteotrophic and luteolytic actions of ovarian peptides. Hum. Reprod. 8(suppl 2):141-146
  52. Wuttke, W., Pitzel, L., Knoke, I., Theiling, K. and Jarry, H. 1997. Immunoendocrine interactions affecting luteal function in pigs. J. Reprod. Fertil. Suppl. 52:19-29
  53. Zhao, Y., Burbach, J. A., Roby, K. F., Terranova, P. F. and Brannian, J. D. 1998. Macrophages are the major source of tumor necrosis factor ${\alpha}$ in the porcine corpus luteum. Biol. Reprod. 59: 1385-1391 https://doi.org/10.1095/biolreprod59.6.1385
  54. Zolti, M., Meirom, R., Shemesh, M., Wollach, D., Mashiach, S., Shore, L. and Ben Rafael, Z. 1990. Granulosa cells as a source and target organ for tumor necrosis factor-${\alpha}$. FEBS Lett. 261:253-255 https://doi.org/10.1016/0014-5793(90)80565-Z
  55. 박창식, 한승로, 김수일, 조근자, 김원식. 돼지난소에서 난포폐쇄시 과립층세포의 아포토시스와 대식세포에 관한 형태학적 연구. 한국동물자원과학회지, 46(4):571-584, 2004