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Granzyme A — Immunoreactive cells in synovial fluid in reactive and rheumatoid arthritis

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Summary

Perforin and granzyme A co-localize in the cytotoxic granules of killer cells like cytotoxic T lymphocytes (CTL). Perforin is the cytolytic pore-forming protein, whereas the function of the homodimeric serine protease granzyme A and other members of the granzyme family is still unclear. Granzyme A — immunoreactive cells formed 8±2% of the resting peripheral blood lymphocytes of healthy individuals. In contrast, granzyme A-positive cells formed 15% of peripheral blood mononuclear cells in patients with reactive or rheumatoid arthritis. However, 29±4% (p<0.05 compared to normal peripheral blood) and 25±4% (p<0.05) of all lymphocytes in synovial fluid in reactive and rheumatoid arthritis, respectively, were granzyme A — positive. This suggests involvement of cell-mediated cytolytic mechanisms in the articular pathogenic mechanisms. This involvement, however, does not differentiate between reactive and rheumatoid arthritis.

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References

  1. Aho, K., Ahvonen, P., Lassus, A., Sievers, K., Tillikainen, A. HL-A antigen 27 and reactive arthritis. Lancet 1973, ii, 157.

    Article  Google Scholar 

  2. Brewerrton, D.A., Caffrey, M., Nicholls, A., Walters, D., Oates, J.K., James, D.C.O., Reiter's disease and HL-A 27 Lancet 1973, ii, 996–98.

    Article  Google Scholar 

  3. Stasny, P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 1978, 298, 869–71.

    Article  Google Scholar 

  4. Gibofsky, A., Winchester, R.J., Patarroyo, M., Fotino, M., Kungel, H.G. Disease associations of the Ia-like human alloantigens. J Exp Med 1978, 148, 1728–32.

    Article  CAS  PubMed  Google Scholar 

  5. Gregerssen, P.K., Silver, J., Winchester, R.J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987, 30, 1205–13.

    Article  Google Scholar 

  6. Keat, A., Thomas, B., Dixey, J., Osborn, M., Sonnex, C., Taylor-Robinson, D. Chlamydia trachomatis and reactive arthritis: the missing link. Lancet 1987, i, 72–74.

    Article  Google Scholar 

  7. Schumacher, H.R. Jr., Magge, S., Cherian, P.V., et al. Light and electron microscopic studies on the synovial membrane in Reiter's syndrome. Immunohistochemical identification of chlamydial antigen in patients with early disease. Arthritis Rheum 1988, 31, 937–946.

    Article  PubMed  Google Scholar 

  8. Granfors, K., Jalkanen, S., Von Essen, R., et al. Yersinia antigens in synovial-fluid cells from patients with reactive arthritis. N Engl J Med 1989, 320, 216–21.

    Article  CAS  PubMed  Google Scholar 

  9. Granfors, K., Jalkanen, S., Lindberg, A.A., et al. Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis. Lancet 1990, i, 685–88.

    Article  Google Scholar 

  10. Viitanen, A-M., Arstila, P., Lahesmaa, R., Gransfors, K., Skurnik, M., Toivanen, P. Application of the polymerase chain reaction and immunofluorescence techniques to the detection of bacteria in yersinia-triggered reactive arthritis. Arthritis Rheum 1991, 34, 89–96.

    Article  CAS  PubMed  Google Scholar 

  11. Ford, D.K., Daroza, D.M., Shati, P., Wenman, W., Cell-mediated immune responses of synovial mononuclear cells in Reiter's syndrome against ureplasmal and chlamydial antigens. J Rheumatol 1980, 7, 751–55.

    CAS  PubMed  Google Scholar 

  12. Gaston, J.S., Life, P.F., Granfors, K., et al. Synovial T lymphocyte recognition of organisms that trigger reactive arthritis. Clin Exp Rheumatol 1989, 76, 348–53.

    CAS  Google Scholar 

  13. Konttinen, Y.T., Nordström, D., Begroth, V., Leirisalo-Repo, M., Skrifvars, B. Cell-mediated immune response in the diseased joints in patients with reactive arthritis. Scand J Immunol 1986, 23, 685–91.

    Article  CAS  PubMed  Google Scholar 

  14. Winchester, R.J. The major histocompatibility complex. In: Textbook of Rheumatology, 3rd ed., Eds: Kelley, W.N., Harris, E.D. Jr., Ruddy, S., Sledge, C.B., Philadelphia, W.B. Saunders, 1989, 101–137.

    Google Scholar 

  15. Winchester, R., Bernstein, D.H., Fisher, H.D., Enlow, R., Solomon, G. The co-occurrence of Reiter's syndrome and acquired immunodeficiency. Ann Intern Med 1987, 106, 19–26.

    Article  CAS  PubMed  Google Scholar 

  16. Jaffe, I.A. Rheumatoid arthritis and AIDS. J Rheumatol 1989, 16, 845.

    Google Scholar 

  17. Masson, D., Tschopp, J. Isolation of a lytic, pore-forming protein (perforin) from cytolytic T-lymphocytes. J Biol Chem 1985, 260, 9069–72.

    CAS  PubMed  Google Scholar 

  18. Podack, E.R., Young, J.D-E., Cohn, Z. Isolation and biochemical and functional characterization of perforin I from cytolytic T-cell granules. Proc Natl Acad Sci 1985, 82, 8629–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pasternack, M.S., Verret, C.R., Liu, M.A., Eisen, H.N. Serine esterase in cytolytic T lymphocytes. Nature 1986, 322, 740–43.

    Article  CAS  PubMed  Google Scholar 

  20. Young, J.D-E., Leong, L.G., Liu, C.C., Damiano, A., Wall, D.A., Cohn, ZA. Isolation and characterization of a serine esterase from cytolytic T cell granules. Cell 1986, 47, 183–94.

    Article  CAS  PubMed  Google Scholar 

  21. Masson, D., Tschopp, J. A family of serine esterases in lytic granules of cytolytic T lymphocytes. Cell 1987, 49, 679–85.

    Article  CAS  PubMed  Google Scholar 

  22. Jenne, D.E., Masson, D., Zimmer, M., Haefliger, J-A., Li, W-H., Tschopp, J. Isolation and complete structure of the lymphocyte serine protease granzyme G, a novel member of the granzyme multigene family in murine cytolytic T lymphocytes. Evolutionary origin of lymphocyte proteases. Biochem 1989, 28, 7953–61.

    Article  CAS  Google Scholar 

  23. Peters, P.J., Geuze, H.J., Van der Donk, H., Borst, J. A new model for lethal hit delivery by cytotoxic T lymphocytes. Immunology Today 1990, 11, 28–32.

    Article  CAS  PubMed  Google Scholar 

  24. Velotti, F., MacDonald, H.R., Nabholz, M. Granzyme A secretion by normal activated Lyt-2+ and L3T4+ T cells in response to antigenic stimulation. Eur J Immunol 1987, 17, 1095–99.

    Article  CAS  PubMed  Google Scholar 

  25. Garcia-Sanz, J.A., Plaetnick, G., Velotti, F., et al. Perforin is present only in normal activated Lyt2+ T lymphocytes and not in L3T4+ cells, but the serine protease granzyme A is made by both subsets. EMBO J 1987, 6, 933–938.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Velotti, F., Palmieri, G., Morrone, S., Piccoli, M., Frati, L., Santori, A. Granzyme A expression by normal rat natural killer (NK) cells in vivo and by interleukin 2- activated NK cells in vitro. Eur J Immunol 1989, 19, 575–78.

    Article  CAS  PubMed  Google Scholar 

  27. Held, W., MacDonald, H.R., Weissman, I.L., Hess, M.W., Muller, C. Genes encoding tumor necrosis factor alpha and granzyme A are expressed during development of autoimmune diabetes. Proc Natl Acad Sci USA 1990, 87, 2239–2243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Muller, C., Kagi, D., Aebisher, T., et al. Detection of perforin and granzyme AmRNA in infiltrating cells during infection of mice with lymphocytic choriomeningitis virus. Eur J Immunol 1989, 19, 1253–59.

    Article  CAS  PubMed  Google Scholar 

  29. Griffiths, G.M., Alpert, S., Lalmbert, E., McGuire, J., Weissman, I. Perforin and granzyme A expression identifying cytolytic lymphocytes in rheumatoid arthritis. Proc Natl Acad Sci (USA) 1992, 89, 549–553.

    Article  CAS  Google Scholar 

  30. Nordström, D.C., Konttinen, Y.T. Reactive arthritis — an update. Biomed & Pharmacother 1989, 43, 737–42.

    Article  Google Scholar 

  31. Konttinen, Y.T., Nordström, D., Bergroth, V., Leirisalo-Repo, M., Santavirta, S. Occurrence of different ensuing triggering infections preceding reactive arthritis: a follow-up study. Br Med J 1988, 296, 1644–45.

    Article  CAS  Google Scholar 

  32. Arnett, F.C., Edworthy, D.A., Bloch, D.J., et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31, 315–24.

    Article  CAS  PubMed  Google Scholar 

  33. Hsu, S-M., Raine, L., Fanger, H. The use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedure. J Histochem Cytochem 1981, 29, 577–80.

    Article  CAS  PubMed  Google Scholar 

  34. Krähenbuhl, O., Rey, C., Jenne, D., et al. Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes. J Immunol 1988, 141, 3471–3477.

    PubMed  Google Scholar 

  35. Liu, C.C., Joang, S.V., Kwon, B.S., Young, J.D. Induction of perforin and serine esterases in a murine cytotoxic T lymphocyte clone. J Immunol 1990, 144, 1196–201.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Inflammation Research Group, Department of Anatomy and Department of Periodontology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland

    T. Sorsa, P. Nykanen & S. Santavirta

  2. Fourth Department of Medicine, Helsinki University Central Hospital, Unionsgatan 38, SF-00170, Helsinki, Finland

    D. C. Nordström & T. Pettersson

  3. Institute of Molecular Immunology, Hospital for Joint Diseases, NYU Medical School, New York, NY, USA

    Y. T. Konttinen

  4. University of Lausanne, Lausanne, Switzerland

    J. Tschopp

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  1. D. C. Nordström
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  2. Y. T. Konttinen
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  7. J. Tschopp
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Nordström, D.C., Konttinen, Y.T., Sorsa, T. et al. Granzyme A — Immunoreactive cells in synovial fluid in reactive and rheumatoid arthritis. Clin Rheumatol 11, 529–532 (1992). https://doi.org/10.1007/BF02283113

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  • DOI: https://doi.org/10.1007/BF02283113

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