Skip to main content
SpringerLink
Log in

Effect of cyclosporine on distribution of macrophage subpopulations in rat hepatic allograft

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Macrophage subpopulations infiltrating the grafts of ACI(RT1a) to LEW(RT11) orthotopic rat liver transplants treated with or without immunosuppressive therapy were studied using immunohistochemical staining. LEW recipients of ACI liver transplants experienced severe acute graft rejection, with a mean survival of only 10.2±0.7 days. An indirect immunoperoxidase technique on cryostat sections of the liver grafts was used to determine the localization of macrophage subpopulations infiltrating the grafts, as defined by specific anti-rat macrophage monoclonal antibodies, designated TRPM-1 (panmacrophage), TRPM-3 (activated macrophage) and Ki-M2R (tissue macrophage). TRPM-1+ or TRPM-3+ cells gradually increased on days 5 and 7 in the untreated hepatic allografts, whereas no significant changes in the number of these cells were observed in the isografts. Treatment with cyclosporine (CsA) greatly decreased the number of these two different types of cells infiltrating the hepatic allografts, compared to the untreated hepatic allografts or the isografts. The time course of the accumulation of these cells in the allografts treated with CsA showed a similar pattern; the cells increased gradually by day 5 and thereafter decreased. This pattern is different from that observed in the untreated allografts or in the isografts. There was no significant difference in the number of Ki-M2R+ cells between the untreated hepatic allografts and the isografts. However, the number of the Ki-M2R+ cells in the hepatic allografts treated with CsA was much less than that of either the untreated allografts or the isografts. These findings suggest that a progressive relative increase in host TRPM-3+ macrophage is a characteristic feature of ongoing first-set rejection in the rat hepatic allograft. The administration of CsA significantly decreased the number of macrophages infiltrating the allograft, even when compared with the isografts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gordon S: Biology of the macrophage. J Cell Sci 4:267–286, 1986

    Google Scholar 

  2. Johnston RB, Jr: Current concepts: Immunology. Monocytes and macrophages. N Engl J Med 318:747–752, 1988

    Google Scholar 

  3. Unanue ER, Allen PM: The basis for the immunoregulatory role of macrophages and other accessory cells. Science 236:551–557, 1987

    Google Scholar 

  4. Dempster WJ: The migrant cells in allotransplants of heart, kidney, and skin. I. A comparative electron microscopic analysis of the migrant cells. Br J Exp Pathol 58:418–433, 1977

    Google Scholar 

  5. Rothwell TLW, Papadimitriou JM: The cellular infiltrate in skin allografts in mice. J Pathol 107:235–243, 1972

    Google Scholar 

  6. Tilney NL: The character of effector cells and the accumulation of macrophages in rejecting heart allografts in the rat. Br J Surg 60:314, 1973 (abstract)

    Google Scholar 

  7. Christmas SE, MacPherson GG: The role of mononuclear phagocytes in cardiac allograft rejection in the rat. II. Characterization of mononuclear phagocytes extracted from rat cardiac allografts. Cell Immunol 69:271–280, 1982

    Google Scholar 

  8. Wight DGD: The morphology of rejection of liver transplants.In Transplantation Immunology: Clinical and Experiments. RY Calne (ed). New York, Oxford University Press, 1984, p 53

    Google Scholar 

  9. Eggink HF, Hofstee N, Gips CH, Krom RA, Houthoff HJ: Histopathology of serial graft biopsies from liver transplant recipients. Am J Pathol 114:18–31, 1984

    Google Scholar 

  10. Tilney NL, Strom TB, Macpherson SG, Carpenter CB: Studies on infiltrating host cells harvested from acutely rejecting rat cardiac allografts. Surgery. 79:209–217, 1976

    Google Scholar 

  11. Strom TB, Tilney NL, Paradysz JM, Bancewicz J, Carpenter CB: Cellular components of allograft rejection: identity, specificity, and cytotoxic function of cells infiltrating acutely rejecting allografts. J Immunol 118:2020–2026, 1977

    Google Scholar 

  12. Tilney NL, Strom TB, MacPherson SG, Carpenter CB: Surface properties and functional characteristics of infiltrating cells harvested from acutely rejecting cardiac allografts in inbred rats. Transplantation 20:323–330, 1975

    Google Scholar 

  13. Wacker HH, Radzun HJ, Parwaresch MR: Ki-M2R, a new specific monoclonal antibody, discriminates tissue macrophages from reticulum cells and monocytesin vivo andin vitro. J Leukocyte Biol 38:509–520, 1985

    Google Scholar 

  14. Takeya M, Hsiao L, Shimokawa Y, Takahashi K. Heterogeneity of rat macrophages recognized by monoclonal antibodies: An immunohistochemical and immunoelectron microscopic study. J Histochem Cytochem 37:635–641, 1989

    Google Scholar 

  15. Takeya M, Hsiao L, Takahashi K: A new monoclonal antibody, TRPM-3, binds specifically to certain rat macrophage populations: Immunohistochemical and immunoelectron microscopic analysis. J Leukocyte Biol 41:187–195, 1987

    Google Scholar 

  16. Yamaguchi Y, Harland RC, Wyble C, Bollinger RR: The role of class I major histocompatibility complex antigens in prolonging the survival of hepatic allografts in the rat. Transplantation 47:171–177, 1989

    Google Scholar 

  17. Public Health Service: Guide for the Care and Use of Laboratory Animals. National Institute of Health, NIH Publication No. 86-2, Bethesda, Maryland, 1985

    Google Scholar 

  18. McLean IW, Nakane PK: Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem 22:1077–1983, 1974

    Google Scholar 

  19. Isobe Y, Chen ST, Nakane PK, Brown WR: Studies on translocation of immunoglobulins across intestinal epithelium. I. Improvements in the peroxidase-labeled antibody method for application to study of human intestinal mucosa. Acta Histochem Cytochem 10:161–171, 1977

    Google Scholar 

  20. Matsuno K, Ezaki T, Kotani M: Splenic outer periarterial lymphoid sheath (PALS): An immuncproliferative microenvironment constituted by antigen-laden marginal metallophils and ED2-positive macrophage in the rat. Cell Tissue Res 257:459–470, 1989

    Google Scholar 

  21. Wight DGD: Pathology of liver transplantationIn Liver Transplantation. RY Calne (ed). London, Grune & Stratton, 1983, p 289

    Google Scholar 

  22. Snover DC, Sibley RK, Freese DK, Sharp HL, Bloomer JR, Najarian JS, Ascher NL: Orthotopic liver transplantation: a pathological study of 63 serial liver biopsies from 17 patients with special reference to the diagnostic features and natural history of rejection. Hepatology 4:1212–1222, 1984

    Google Scholar 

  23. Demetris AJ, Lasky S, van Thiel DH, Starzl TE, Dekker A: Pathology of hepatic transplantation: A review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid regimen. Am J Pathol 118:151–161, 1985

    Google Scholar 

  24. Williams JW, Peters TG, Vera SR, Britt LG, van Voorst SJ, Haggitt RC: Biopsy-directed immunosuppression following hepatic transplantation in man. Transplantation 39:589–596, 1985

    Google Scholar 

  25. Porter KA: The pathology of rejection in human liver allografts. Transplant Proc 20:483–484, 1988

    Google Scholar 

  26. Balch CM, Wilson CB, Lee S, Feldman JD: Thymusdependent lymphocytes in tissue sections of rejecting renal allografts. J Exp Med 138:1584–1590, 1973

    Google Scholar 

  27. Strom TB, Tilney NL, Carpenter CB, Bush GJ: Identity and cytotoxic capacity of cells infiltrating renal allografts. N Engl J Med 292:1257–1263, 1975

    Google Scholar 

  28. Ishikura H, Matsuura A, Ishii Y, Natori T, Kikuchi K, Aizawa M: Different distributions of T cell subsets between perivascular and interstitial peritubular areas during rejection of rat renal allografts: A quantitative and ultrastructural study using monoclonal antibodies. Clin Exp Immunol 62:570–578, 1985

    Google Scholar 

  29. Forbes RD, Guttmann RD, Gomersall M, Hibberd J: Leukocyte subsets in first-set rat cardiac allograft rejection. A serial immunohistologic study using monoclonal antibodies. Transplantation 36:681–686, 1983

    Google Scholar 

  30. Platt JL, LeBien TW, Michael AF: Interstitial mononuclear cell populations in renal allograft rejection. Identification by monoclonal antibodies in tissue sections. J Exp Med 155:17–30, 1982

    Google Scholar 

  31. von Willebrand E, Hayry P: Composition andin vitro cytotoxicity of cellular infiltrates in rejecting human kidney allografts. Cell Immunol 41:358–372, 1978

    Google Scholar 

  32. debray-Sachs M, Descamps B: Role of macrophages in allograft rejection. Transplant Proc 11:811–812, 1979

    Google Scholar 

  33. Andreesen R, Boyce NM, Atkins RC: The expression of specific differentiation antigens on macrophages infiltrating rejecting renal allografts. Transplant Proc 19:2885–2886, 1987

    Google Scholar 

  34. Gassel AM, Radzun ML, Harsman H-J, Weyand M, Konertz W: Monocytes and macrophages in the rejection of human cardiac allografts. Transplant Proc 21:2514–2516, 1989

    Google Scholar 

  35. Shevach EM: The effects of cyclosporin A on the immune system. Annu Rev Immunol 3:397–423, 1985

    Google Scholar 

  36. Knight SC, Balfour B, O'Brien J, Buttifant L: Sensitivity of veiled (dendritic) cells to cyclosporine. Transplantation 41:96–100, 1986

    Google Scholar 

  37. Varey A, Champion BR, Cooke A: Cyclosporine affects the function of antigen presenting cells. Immunology 57:111–114, 1986

    Google Scholar 

  38. Manca F, Kunkl A, Celada F: Inhibition of the accessory function of murine macrophagesin vitro by cyclosporine. Transplantation 39:644–649, 1985

    Google Scholar 

  39. Palay DA, Cluff CW, Wentworth PA, Ziegler HK: Cyclosporine inhibits macrophage-mediating antigen presentation. J Immunol 136:4348–4353, 1986

    Google Scholar 

  40. Knight SC, Roberts M, Macatonia SE, Edwards AJ: Blocking of acquisition and presentation of antigen by dendritic cells with cyclosporine. Studies with fluorescein isothiocyanate. Transplantation 46:48–53, 1988

    Google Scholar 

  41. Hanto DW, Hardy JT, Hoffman RA, Simmons RL: Evidence that secondary mixed leukocyte culture supernatant mediates changes in cellular recruitment, blood flow, and vascular permeability. Transplantation 42:621–627, 1986

    Google Scholar 

  42. Kahan BD: Cyclosporine. N Engl J Med 21:1725–1738, 1989

    Google Scholar 

  43. Pearson LD, Osebold JW: Effects of antilymphocyte sera and antimacrophage sera on cell-mediated immune reactions in Listeria-infected mice. Infect Immunol 9:127–133, 1974

    Google Scholar 

  44. Dyminski JW, Argyrus BF: Prolongation of allograft survival with antimacrophage serum. Transplantation 8:595–601, 1969

    Google Scholar 

  45. Cameron DJ, Rajagopalan PR: Failure of antimacrophage globulin to prolong mouse skin allografts. Transplantation 31:299–302, 1981

    Google Scholar 

  46. Feldman JD, Tubergen DG, Pollock EM, Unanue ER: Distribution of a macrophage-specific antigen. Cell Immunol 5:325–337, 1972

    Google Scholar 

  47. Christmas SE, MacPherson GG: The role of mononuclear phagocytes in cardiac allograft rejection in the rat. I. Ultrastructural and cytochemical features. Cell Immunol 69:248–270, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Second Department of Pathology, Kumamoto University Medical School, Kumamoto, Japan

    Yasuo Yamaguchi MD, Mikio Misumi MD, Katsutaka Mori MD, Noboru Takata MD, Matarou Goto MD, Yasuhiro Makino MD, Nobuyki Kikuchi MD, Hiromitsu Hamaguchi MD, Naoya Hisama MD, Motohiro Takeya MD, Makoto Naito MD, Kiyoshi Takahashi MD &  Michio Ogawa MD

  2. Second Department of Surgery, Kumamoto University Medical School, Honjo 1-1-1, 860, Kumamoto, Japan

    Yasuo Yamaguchi MD, Mikio Misumi MD, Katsutaka Mori MD, Noboru Takata MD, Matarou Goto MD, Yasuhiro Makino MD, Nobuyki Kikuchi MD, Hiromitsu Hamaguchi MD, Naoya Hisama MD, Motohiro Takeya MD, Makoto Naito MD, Kiyoshi Takahashi MD &  Michio Ogawa MD

Authors
  1. Yasuo Yamaguchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mikio Misumi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katsutaka Mori MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Noboru Takata MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matarou Goto MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuhiro Makino MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nobuyki Kikuchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiromitsu Hamaguchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Naoya Hisama MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Motohiro Takeya MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Makoto Naito MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kiyoshi Takahashi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michio Ogawa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamaguchi, Y., Misumi, M., Mori, K. et al. Effect of cyclosporine on distribution of macrophage subpopulations in rat hepatic allograft. Digest Dis Sci 38, 619–625 (1993). https://doi.org/10.1007/BF01316790

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01316790

Key Words

Search

Navigation