Rheumatology International

, Volume 7, Issue 1, pp 35–41 | Cite as

Diverse morphological responses of normal human synovial fibroblasts to mononuclear leukocyte products: relationship to prostaglandin production and plasminogen activator activities, and comparison with the effects of purified interleukin 1

  • B. J. Clarris
  • T. Leizer
  • J. R. E. Fraser
  • J. A. Hamilton


Supernatant media from cultured human mononuclear blood leukocytes (MCCM) induced morphological changes in normal human synovial fibroblasts in culture, including the formation of cells with a dendritic or stellate morphology and, less frequently, cells with a striking fenestrated appearance. These changes were fully reversed within 1 h of removing the MCCM. They were inhibited by indomethacin, the glucocorticoids hydrocortisone, prednisolone and dexamethasone, and by colcemid, but not by actinomycin D and only weakly by cycloheximide. The morphological responses to MCCM could be reproduced by MCCM fractions containing interleukin 1-like activity and by purified forms of human interleukin 1 (IL-1), including monocyte-derived IL-1β and recombinant IL-1α. These responses were also inhibited by indomethacin, indicating a link with prostanoid production. However, the morphological responses were not related to the stimulation of plasminogen activator activity due to MCCM, MCCM fractions, or IL-1.

Key words

Synovial fibroblasts Morphology Prostanoids Mononuclear cells Interleukin 1 


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  1. 1.
    Bromley M, Wooley DE (1984) Histopathology of the rheumatoid lesion. Identification of cell types at sites of cartilage erosion. Arthritis Rheum 27:857–863Google Scholar
  2. 2.
    Dayer J-M, Krane SM, Russell RGG, Robinson DR (1976) Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. Proc Natl Acad Sci USA 73:945–949Google Scholar
  3. 3.
    Dayer J-M, Breard J, Chess L, Krane SM (1979) Participation of monocyte-macrophages and lymphocytes in the production of a factor that stimulates collagenase and prostaglandin release by rheumatoid synovial cells. J Clin Invest 64:1386–1392Google Scholar
  4. 4.
    Woolley DE, Brinckerhoff CE, Mainardi CL, Vater CA, Evanson JM, Harris ED Jr (1979) Collagenase production by rheumatoid synovial cells: morphological and immunohistochemical studies of the dendritic cell. Ann Rheum Dis 38:262–270Google Scholar
  5. 5.
    Baker DG, Dayer J-M, Roelke M, Schumacher HR, Krane SM (1983) Rheumatoid synovial cell morphologic changes induced by a mononuclear cell factor in culture. Arthritis Rheum 26:8–14Google Scholar
  6. 6.
    Fraser JRE, Clarris BJ, Baxter E (1979) Patterns of induced variation in the morphology, hyaluronic acid secretion, and lysosomal enzyme activity of cultured human synovial cells. Ann Rheum Dis 38:287–294Google Scholar
  7. 7.
    Clarris BJ (1982) Morphological effects of prostaglandins E1, E2 and F2a on fibroblast-like cultures of human synovial cells. Experientia 38:350–351Google Scholar
  8. 8.
    Hamilton JA, Slywka J (1981) Stimulation of human synovial fibroblast plasminogen activator production by mononuclear cell supernatants. J Immunol 126:851–855Google Scholar
  9. 9.
    Hamilton JA (1983) Hypothesis. In vitro evidence for the invasive and tumor-like properties of the rheumatoid pannus. J Rheumatol 10:845–851Google Scholar
  10. 10.
    Leizer T, Clarris BJ, Ash PE, Van Damme J, Saklatvala J, Hamilton JA (1987) Interleukin-1β and interleukin-1α stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells. Arthritis Rheum (in press)Google Scholar
  11. 11.
    Fontana A, Hengartner H, Weber E, Fehr K, Grob PJ, Cohen G (1982) Interleukin-1 activity in the synovial fluid of patients with rheumatoid arthritis. Rheumatol Int 2:49–53Google Scholar
  12. 12.
    Fraser JRE, Catt KJ (1961) Human synovial cell culture. Use of a new method in a study of rheumatoid arthritis. Lancet II:1437–1439Google Scholar
  13. 13.
    Clarris BJ, Fraser JRE (1968) Relationship between chromosomal changes and alterations in the behaviour of a strain of human synovial cells during its life history in vitro. Ann Rheum Dis 27:597–603Google Scholar
  14. 14.
    Ossowski L, Quigley JP, Reich E (1981) Fibrinolysis associated with oncogenic transformation. Morphological correlates. J Biol Chem 249:4312–4320Google Scholar
  15. 15.
    Deutsch DG, Mertz J (1970) Plasminogen purification from human plasma by affinity chromatography. Science 170:1095–1096Google Scholar
  16. 16.
    Gubler U, Chua AO, Stern AS, Hellmann CP, Vitek MP, Dechiara TM, Benjamin WR, Collier KJ, Dukovich M, Familotti PC, Fiedler-Nagy C, Jenson J, Kaffka K, Killian PL, Stremol D, Wittereich BH, Woehle D, Mizel SB, Lomedico PT (1986) Recombinant human interleukin 1α: purification and biological characterization. J Immunol 136:2492–2497Google Scholar
  17. 17.
    Rosenwasser CJ, Dinarello CA (1981) Ability of human leukocytic pyrogen to enhance phytohemagglutinin-induced murine thymocyte proliferation. Cell Immunol 63:134–142Google Scholar
  18. 18.
    Hamilton JA (1983) Synovial cell activation. Studies on the mechanism of action of synovial activator activity. J Rheumatol 10:872–880Google Scholar
  19. 19.
    Clarris BJ, Hamilton JA (1985) Peripheral blood mononuclear cells stimulate N-acetyl-β-glucosaminidase levels of human synovial fibroblast-like cells. Rheumatol Int 5:55–60Google Scholar
  20. 20.
    Hamilton JA, Zabriskie JB, Lachman LB, Chen Y-S (1982) Streptococcal cell walls and synovial cell activation. J Exp Med 155:1702–1718Google Scholar
  21. 21.
    Lachman LB, Page SO, Metzgar RS (1980) Purification of human interleukin-1. J Supramol Struct 13:457–462Google Scholar
  22. 22.
    Hamilton JA (1982) Plasminogen activator activity of rheumatoid and non-rheumatoid synovial fibroblasts. J Rheumatol 9:834–842Google Scholar
  23. 23.
    Medcalf RL, Hamilton JA (1986) Human synovial fibroblasts produce urokinase-type plasminogen activator. Arthritis Rheum 29:1397–1401Google Scholar
  24. 24.
    Hamilton JA (1982) Stimulation of the plasminogen activator activity of human synovial fibroblasts by retinoids. Arthritis Rheum 25:432–440Google Scholar
  25. 25.
    Clarris BJ, Fraser JRE, Baxter E, Malcolm LP (1979) Effects of carrageenin on human synovial cells in vitro: morphology, hyaluronic acid production, growth, and the lysosomal system. Ann Rheum Dis 38:295–298Google Scholar
  26. 26.
    Dayer J-M, Beutler B, Cerami A (1985) Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med 162:2163–2168Google Scholar
  27. 27.
    Dower SK, Call SM, Gillis D, Urdal DL (1986) Similarity between the interleukin-1 receptors on a murine T-lymphoma cell line and on a murine fibroblast cell line. Proc Natl Acad Sci USA 83:1060–1064Google Scholar
  28. 28.
    March CJ, Mosley D, Larson A, Cerretti DP, Braedt G, Price V, Gillis S, Henney CS, Kronheim SR, Grabstein K, Conlon PJ, Hopp TP, Cosman D (1985) Cloning sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315:641–647Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • B. J. Clarris
    • 1
  • T. Leizer
    • 1
  • J. R. E. Fraser
    • 1
  • J. A. Hamilton
    • 1
  1. 1.Department of Medicine, Royal Melbourne HospitalUniversity of MelbourneParkvilleAustralia

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