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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

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Summary

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.

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References

  1. Bromley M, Wooley DE (1984) Histopathology of the rheumatoid lesion. Identification of cell types at sites of cartilage erosion. Arthritis Rheum 27:857–863

    Google Scholar 

  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 73:945–949

    Google Scholar 

  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 64:1386–1392

    Google Scholar 

  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 38:262–270

    Google Scholar 

  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 26:8–14

    Google Scholar 

  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 38:287–294

    Google Scholar 

  7. Clarris BJ (1982) Morphological effects of prostaglandins E1, E2 and F2a on fibroblast-like cultures of human synovial cells. Experientia 38:350–351

    Google Scholar 

  8. Hamilton JA, Slywka J (1981) Stimulation of human synovial fibroblast plasminogen activator production by mononuclear cell supernatants. J Immunol 126:851–855

    Google Scholar 

  9. Hamilton JA (1983) Hypothesis. In vitro evidence for the invasive and tumor-like properties of the rheumatoid pannus. J Rheumatol 10:845–851

    Google Scholar 

  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)

  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 2:49–53

    Google Scholar 

  12. Fraser JRE, Catt KJ (1961) Human synovial cell culture. Use of a new method in a study of rheumatoid arthritis. Lancet II:1437–1439

    Google Scholar 

  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 27:597–603

    Google Scholar 

  14. Ossowski L, Quigley JP, Reich E (1981) Fibrinolysis associated with oncogenic transformation. Morphological correlates. J Biol Chem 249:4312–4320

    Google Scholar 

  15. Deutsch DG, Mertz J (1970) Plasminogen purification from human plasma by affinity chromatography. Science 170:1095–1096

    Google Scholar 

  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 136:2492–2497

    Google Scholar 

  17. Rosenwasser CJ, Dinarello CA (1981) Ability of human leukocytic pyrogen to enhance phytohemagglutinin-induced murine thymocyte proliferation. Cell Immunol 63:134–142

    Google Scholar 

  18. Hamilton JA (1983) Synovial cell activation. Studies on the mechanism of action of synovial activator activity. J Rheumatol 10:872–880

    Google Scholar 

  19. Clarris BJ, Hamilton JA (1985) Peripheral blood mononuclear cells stimulate N-acetyl-β-glucosaminidase levels of human synovial fibroblast-like cells. Rheumatol Int 5:55–60

    Google Scholar 

  20. Hamilton JA, Zabriskie JB, Lachman LB, Chen Y-S (1982) Streptococcal cell walls and synovial cell activation. J Exp Med 155:1702–1718

    Google Scholar 

  21. Lachman LB, Page SO, Metzgar RS (1980) Purification of human interleukin-1. J Supramol Struct 13:457–462

    Google Scholar 

  22. Hamilton JA (1982) Plasminogen activator activity of rheumatoid and non-rheumatoid synovial fibroblasts. J Rheumatol 9:834–842

    Google Scholar 

  23. Medcalf RL, Hamilton JA (1986) Human synovial fibroblasts produce urokinase-type plasminogen activator. Arthritis Rheum 29:1397–1401

    Google Scholar 

  24. Hamilton JA (1982) Stimulation of the plasminogen activator activity of human synovial fibroblasts by retinoids. Arthritis Rheum 25:432–440

    Google Scholar 

  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 38:295–298

    Google Scholar 

  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 162:2163–2168

    Google Scholar 

  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 83:1060–1064

    Google Scholar 

  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 315:641–647

    Google Scholar 

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Clarris, B.J., Leizer, T., Fraser, J.R.E. et al. 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. Rheumatol Int 7, 35–41 (1987). https://doi.org/10.1007/BF00267340

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