Rheumatology International

, Volume 3, Issue 3, pp 133–138 | Cite as

The effect of rheumatoid synovial fluid macrophages on DNA, glycosaminoglycan and collagen synthesis by synovial fibroblasts

  • K. Pulkki
  • E. Vuorio
  • S. Jalava


The effects of soluble factors secreted by peripheral blood monocytes and rheumatoid synovial fluid macrophages were tested on human synovial fibroblast cultures. Both monocytes and macrophages liberated factors which reduced DNA synthesis (3H-thymidine incorporation) by synovial fibroblasts. Monocyte and macrophage factors stimulated hyaluronic acid synthesis. The activation obtained with rheumatoid synovial macrophages was considerably greater than that with monocytes. Foetal bovine serum was found to have a clear stimulatory effect on the synthesis of collagen and other proteins by fibroblasts. The effects of monocyte and macrophage factors on protein synthesis in synovial fibroblasts were small: collagen synthesis was slightly increased relative to other extracellular proteins.

Key words

Monocyte Macrophage Fibroblast Collagen Hyaluronic acid 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Snyderman R, McCarty GA (1978) The role of macrophage in the rheumatic disease. Clin Rheum Dis 4:499–515Google Scholar
  2. 2.
    Diegelmann RF, Cohen IK, Kaplan AM (1981) The role of macrophages in wound repair. Plast Reconstr Surg 68:107–113Google Scholar
  3. 3.
    Seppälä P (1964) Synovial fluid in rheumatoid arthritis. Scand J Clin Lab Invest 16 (Suppl 79):1–107Google Scholar
  4. 4.
    Vuorio E (1977) Rheumatoid disease in cultured human synovial cells. Scand J Clin Lab Invest 37 (Suppl 149):1–72Google Scholar
  5. 5.
    Swann DA, Slayter HS, Silver FH (1981) The molecular structure of lubricating glacoprotein-I, the boundary lubricant for articular cartilage. J Biol Chem 256:5921–5925Google Scholar
  6. 6.
    Vuorio E, Einola S, Hakkarainen S, Penttinen R (1982) Synthesis of underpolymerized hyaluronic acid by fibroblasts cultured from rheumatoid and non-rheumatoid synovitis. Rheumatol Int 2:97–102Google Scholar
  7. 7.
    Castor CW (1975) Synovial cell activation induced by a polypeptide mediator. Ann NY Acad Sci 256:304–317Google Scholar
  8. 8.
    Daireaux M, Penfornis H, Langris M, Bocquet J, Pujol J, Beliard R, Loyau G (1981) Effect of a mononuclear cell culture medium on collagen and glycosaminoglycan production by synovial cells in culture. FEBS Lett 132:93–97Google Scholar
  9. 9.
    Casey WJ, Peacock EE Jr, Chvapil M (1976) Induction of collagen synthesis in rats by transplantation of allogenic macrophages. Surg Forum 27:53Google Scholar
  10. 10.
    Aalto M, Potila M, Kulonen E (1976) The effects of silica-treated macrophages on the synthesis of collagen and other proteins in vitro. Exp Cell Res 97:193–202Google Scholar
  11. 11.
    Jimenez SA, McArthur W, Rosenbloom J (1979) Inhibition of collagen synthesis by mononuclear cell supernates. J Exp Med 150:1421–1431Google Scholar
  12. 12.
    Aalto M, Kulonen E, Rönnemaa T, Sundström C, Vilpo J (1980) Liberation of a fibrogenic factor from human blood monocytes, ascites cells, cultured histiocytes and transformed mouse macrophages by treatment with SiO2. Scand J Clin Lab Invest 40:311–318Google Scholar
  13. 13.
    Viljanto J, Raekallio J (1976) Wound healing in children as assessed by the CELLSTIC method. J Pediatr Surg 11:43–49Google Scholar
  14. 14.
    Pertoft H, Johnsson A, Wärmeg»rd B, Seljelid R (1980) Separation of human monocytes on density gradients by Percoll(R). J Immunol Methods 33:221–229Google Scholar
  15. 15.
    De Jong MCJM (1979) Esterase staining of human peripheral blood mononuclear cells. J Immunol Methods 26:193–196Google Scholar
  16. 16.
    Chen TR (1977) In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res 104:255–262Google Scholar
  17. 17.
    Jalkanen M, Peltonen J, Kulonen E (1979) Isoelectric focusing of macrophage culture media and the effects of the fractions on the synthesis of DNA and collagen by fibroblasts. Acta Pathol Microbiol Scand 87:347–352Google Scholar
  18. 18.
    Saarni H, Tammi M (1977) A rapid method for separation and assay of radiolabeled mucopolysaccharides from cell culture medium. Anal Biochem 81:40–46Google Scholar
  19. 19.
    Jalkanen M, Tammi M, Vihersaari T, Peltonen J, Kulonen E, Penttinen R (1980) A rapid assay to measure collagen synthesis in cell cultures. J Biochem Biophys Methods 2:331–339Google Scholar
  20. 20.
    Morahan PS (1980) Macrophage nomenclature. J Reticuloendothel Soc 27:223–245Google Scholar
  21. 21.
    van Furth R (1981) Phagocytes in normal and inflamed joints. Scand J Rheumatol 11 (Suppl 40):13–20Google Scholar
  22. 22.
    Ziff M (1981) Phagocytes and substrates in the joint. Scand J Rheumatol 11 (Suppl 40):10–12Google Scholar
  23. 23.
    Calderon J, Williams RT, Unanue ER (1974) An inhibitor of cell proliferation released by cultures of macrophages. Proc Natl Acad Sci USA 71:4273–4277Google Scholar
  24. 24.
    Korn JH, Halushka PV, LeRoy EC (1980) Mononuclear cell modulation of connective tissue function. J Clin Invest 65:543–554Google Scholar
  25. 25.
    Leibovich SJ, Ross R (1976) A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am J Pathol 84:501–513Google Scholar
  26. 26.
    Krane SM, Goldring SR, Dayer J-M (1982) Interactions among lymphocytes, monocytes, and other synovial cells in the rheumatoid synovium. In: Pick E (ed) Lymphokines, vol 7. Academic Press, New York London, pp 75–136Google Scholar
  27. 27.
    Antoniades HN, Scher CD, Stiles CD (1979) Purification of human platelet-derived growth factor. Proc Natl Acad Sci USA 76:1809–1813Google Scholar
  28. 28.
    Sloan TB, Weiss JJ, Anderson B, Ritchie JC, Whitney SL, Castor CW (1980) Connective tissue activation XVI. Detection of a human platelet-derived connective tissue activating peptide (CTAP-III) in human sera and plasma and in synovial fluids and tissues. Proc Soc Exp Biol Med 164:267–274Google Scholar
  29. 29.
    Steinberg J (1978) Collagen turnover and the growth state in 3T6 fibroblast cultures. Lab Invest 39:491–4Google Scholar
  30. 30.
    Dayer J-M, Byrne MH, Krane SM (1980) Effects of mononuclear cell factor (MCF), indomethacin and prostaglandin E2 (PGE2) on collagen and fibronectin synthesis by cultured rheumatoid synovial cells. Clin Res 28:343Google Scholar
  31. 31.
    Jalkanen M, Penttinen R (1982) Enhanced fibroblast collagen production by a macrophage-derived factor (CEMF). Biochem Biophys Res Commun 108:447–453Google Scholar
  32. 32.
    Mizel SB, Dayer J-M, Krane SM, Mergenhagen SE (1981) Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin I). Proc Natl Acad Sci USA 78: 2474–2477Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • K. Pulkki
    • 1
  • E. Vuorio
    • 1
  • S. Jalava
    • 2
  1. 1.Department of Medical ChemistryUniversity of TurkuTurku 52Finland
  2. 2.Department of Medicine (Paimio Hospital)University Central Hospital of TurkuTurku 52Finland

Personalised recommendations