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Rheumatology International

, Volume 13, Issue 6, pp 221–228 | Cite as

Phagocytic synovial lining cells in experimentally induced chronic arthritis: down-regulation of synovitis by CL2MDP-liposomes

  • P. L. E. M. Van Lent
  • L. A. M. Van den Bersselaar
  • A. E. M. Holthuyzen
  • N. Van Rooijen
  • L. B. A. Van de Putte
  • W. B. Van den Berg
Originals

Summary

Chronic inflammation of the joint is characterized by the long-term presence of macrophage-like cells in the multilayered synovium. We examined whether synovial phagocytic cells which have settled in the inflamed lining layer play a role in perpetuating synovitis by selectively eliminating them from chronically arthritic murine knee joints. For this purpose we used liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP, Clodronate). Injection of CL2MDP-liposomes into acutely inflamed knee joints (6h, 1 and 3 days) had no significant effect on late chronic synovitis (14 and 21 days after arthritis induction) as observed in haematoxylin and eosin-stained total knee joint sections. Liposomes did not reach the lining layer, as seen with fluorescent liposomes. Additional in vitro studies revealed that activated polymorphs were not affected by CL2MDP-liposomes within 16 h of incubation. Liposomes formed clusters, however, in the presence of intact polymorphs or extracts of polymorphs. In contrast, a significant down-regulation of late synovitis was observed if CL2MDP-liposomes were given during the chronic phase (day 7). Phosphate-buffered saline (PBS) alone or PBS-liposomes had no effect on synovitis. A single injection of CL2MDP-liposomes eliminated many of the phagocytic lining cells and deeper lying inflammatory cells for at least 4 weeks. Free CL2MDP had a minor but significant effect. This study indicates that phagocytic synovial lining cells play an important role in propagating chronic synovitis. To eliminate them from inflamed knee joints, CL2MDP-liposomes should be injected in the chronic and not in the early arthritic phase.

Key words

Arthritis Dichloromethylene diphosphonate Synovial lining cells 

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References

  1. 1.
    Dreher R (1982) Origin of synovial type A cells during inflammation, an experimental approach. Immunobiology 161:232–245Google Scholar
  2. 2.
    Henderson B (1988) The synovial lining cell and synovitis. Scand J Rheumatol Suppl 76:33–38Google Scholar
  3. 3.
    Van Lent PLEM, Van den Bersselaar L, Van den Hoek AEM, Van de Ende M, Dijkstra CD, Van Rooijen N, Van den Berg WB (1993) Reversible depletion of synovial lining cells after intraarticular treatment with liposome encapsulated dichloro-methylene diphosphonate. Rheumatol Int 13:21–30Google Scholar
  4. 4.
    Van Lent PLEM, Van den Hoek AEM, Van den Bersselaar LAM, Spanjaards MFR, Van Rooijen N, Dijkstra CD, Van de Putte LBA, Van den Berg WB (1993) In vivo role of phagocytic lining cells in onset of experimental arthritis. Am J Pathol 143:1226–1237Google Scholar
  5. 5.
    Revell PA (1989) Synovial lining cells. Rheumatol Int 9:49–51Google Scholar
  6. 6.
    Wood DD, Ihrie EJ, Hamerman D (1985) Release of IL-1 from human synovial tissue in vitro. Arthritis Rheum 28:853–862Google Scholar
  7. 7.
    Danis VA, March LM, Nelson DA, Brooks PM (1987) Interleukin-1 secretion by peripheral blood monocytes and synovial macrophages from patients with rheumatoid arthritis. J Rheumatol 14:33–39Google Scholar
  8. 8.
    Dayer JM, 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
  9. 9.
    Vilcek J, Palombella VJ, Henriksen-Destefano D, Swenson C, Feinman R, Hirai M, Tsujimoto M (1986) Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med 163:632–664Google Scholar
  10. 10.
    Schroder JM, Sticherling M, Henneick HM, Preissner WC, Christophers E (1990) IL-1α or tumor necrosis factor α stimulate release of three NAP-1/IL-8 related neutrophil chemotactic proteins in human dermal fibroblasts. J Immunol 144:2223–2232Google Scholar
  11. 11.
    Matsushima K, Oppenheim JJ (1989) Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL-1 and TNF. Cytokine 1:2–13Google Scholar
  12. 12.
    Nakagawa H, Miyai H, Hirata M, Watanabe K, Onuma I (1989) Synergism between interleukin-1β and tumor necrosis factor-α in production by 3T3 cells of a chemotactic factor for rat polymorphonuclear leucocytes. Inflammation 13:553–559Google Scholar
  13. 13.
    Moser R, Schlieffenbaum B, Groscurth P, Fehr J (1989) Interleukin 1 and tumor necrosis factor stimulate human vesicular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest 83:444–455Google Scholar
  14. 14.
    Westwick J, Li SW, Camp RD (1989) Novel neutrophil-stimulating peptides. Immunol Today 10:146–147Google Scholar
  15. 15.
    Fava RA, Olsen NJ, Postlethwaite AE, Broadley KN, Davidson JM, Nanney LB, Lucas C, Townes AS (1991) Transforming growth factor β1 (TGFβ1) induced neutrophil recreatment to synovial tissues: implications for TGFβ driven synovial inflammation and hyperplasia. J Exp Med 173:1121–1132Google Scholar
  16. 16.
    Wahl SM, Hunt DA, Wakefield L McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB (1987) Transforming growth factor beta (TGFβ) induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 84:5788–5792Google Scholar
  17. 17.
    Adams DH, Hathaway M, Shaw J, Burnett D, Elias E, Strain AJ (1991) Transforming growth factor-β induces human T lymphocyte migration in vitro. J Immunol 147:609–612Google Scholar
  18. 18.
    Caputi RA (1988) Synovectomy. Clin Pediatr Surg 5:249–257Google Scholar
  19. 19.
    Boerbooms AMT, Buys WGAM, Danen M, Van de Putte LBA, Van der Broucke JP (1985) Radio-synovectomy in chronic synovitis of the knee joint in patients with rheumatoid arthritis. Eur J Nucl Med 10:446–449Google Scholar
  20. 20.
    Okada Y, Nakanishi I, Kajikawa K (1984) Repair of the mouse synovial membrane after chemical synovectomy with osmium tetroxide. Acta Pathol Jpn 43:705–714Google Scholar
  21. 21.
    Meyers SL, Slowman SD, Brandt KD (1989) Radiation synovectomy stimulates glycoaminoglycan synthesis by normal articular cartilage. J Lab Clin Med 114:27–35Google Scholar
  22. 22.
    Van Rooijen N, Claassen E (1988) In vivo elimination of macrophages in spleen and liver, using liposome-encapsulated drugs: methods and application. In: Gregoriades G (ed) Liposome as drug carriers. Wiley, London, p 131Google Scholar
  23. 23.
    Van Rooijen N (1989) The liposome-mediated macrophage ‘suicide’ technique. J Immunol Methods 124:1–6Google Scholar
  24. 24.
    Hunter WM, Greenwood FC (1962) Preparation of 131I labeled growth hormone of high specific activity. Nature 194:495–496Google Scholar
  25. 25.
    Van Lent PLEM, Van den Berg WB, Schalkwijk J, Van de Putte LBA, Van den Bersselaar L (1987) Allergic arthritis induced by cationic antigens: relationship of chronicity with antigen retention and T cell reactivity. Immunology 62:265–272Google Scholar
  26. 26.
    Claassen E (1991) Post formation fluorescent labeling of liposomal membranes: in vivo detection, localization and kinetics. J Immunol Methods 147:231–240Google Scholar
  27. 27.
    Van den Berg WB, Van de Putte LBA, Zwarts WA, Joosten LAB (1984) Electrical charge of the antigen determines intraarticular handling and chronicity in mice. J Clin Invest 74:1850–1859Google Scholar
  28. 28.
    Rijntjes HVM, Van de Putte LBA, Van der Pol M, Guelen PJM (1979) Cryosectioning of undecalcified tissues for immunofluorescence. J Immunol Methods 30:263–268Google Scholar
  29. 29.
    Middleton MM, Campbell PA (1989) Functions of purified mouse neutrophils isolated from gelatin sponges. J Leuk Biol 46:461–466Google Scholar
  30. 30.
    Van Rooijen N, Van Nieuwmegen R, Kamperdijk EWA (1985) Elimination of phagocytic cells in the spleen after intravenous injection of liposome encapsulated dichloromethylene diphosphonate. Ultrastructural aspects of elimination of marginal zone macrophages. Virchows Arch [B] 49:375–383Google Scholar
  31. 31.
    Delemarre FGA, Kors N, Kraal G, Van Rooijen N (1990) Repopulation of macrophages in popliteal lymph nodes of mice after liposome-mediated depletion. J Leucocyte Biol 47:251–257Google Scholar
  32. 32.
    Bogers WMJM, Stad RK, Janssen DJ, Prins FA, Van Rooijen N, Van Es LA, Daha MR (1991) Kupffer cell depletion in vivo, results in clearance of large sized IgA aggregates in rats by liver endothelial cells. Clin Exp Immunol 85:128–136Google Scholar
  33. 33.
    Thepen T, Van Rooijen N, Kraal G (1989) Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune responses in mice. J Exp Med 170:499–509Google Scholar
  34. 34.
    Claassen E (1992) Detection, localization and kinetics of immunomodulating liposomes in vivo. Res Immunol 143:235–241Google Scholar
  35. 35.
    Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson MP, Haslett C (1989) Macrophage phagocytosis of aging neutrophils in inflammation. J Clin Invest 83:865–875Google Scholar
  36. 36.
    Yoshimura T, Sone S (1987) Different and synergistic actions of human necrosis factor and interferon gamma in damage of liposome membranes. J Biol Chem 262:4597–4601Google Scholar
  37. 37.
    Van Rooijen N (1991) Extracellular and intracellular action of clodronate in osteolytic bone diseases: a hypothesis. Calcif Tissue Int 52:407–410Google Scholar
  38. 38.
    Delaisse JM, Eeckhout Y, Vaes G (1985) Bisphosphonates and bone resorption: effects on collagenase and lysosomal enzyme excretion. Life Sci 37:2291–2256Google Scholar
  39. 39.
    Felix R, Bettex JD, Fleisch H (1981) Effect of diphosphonates on the synthesis of prostaglandins in cultured calvaria cells. Calcif Tissue Int 33:549–552Google Scholar
  40. 40.
    Lens JW, Van den Berg WB, Van de Putte LBA (1984) Flare-up of antigen-induced arthritis in mice after challenge with intravenous antigen. Studies on the characteristics of and mechanisms involved in the reaction. Clin Exp Immunol 55:287–294Google Scholar
  41. 41.
    Lens JW, Van den Berg WB, Van de Putte LBA, Berden JHM, Lems SPM (1984) Flare-up of antigen-induced arthritis in mice after challenge with intravenous antigen: effects of pretreatment with cobra venom factor and antilymphocyte serum. Clin Exp Immunol 57:520–528Google Scholar
  42. 42.
    Lens JW, Van den Berg WB, Van de Putte LBA, Van den Berssclaar L (1984) Flare-up of antigen-induced arthritis in mice after challenge with oral antigen. Clin Exp Immunol 58:364–371Google Scholar
  43. 43.
    Wahl SM, Allen JB, Wong HL, Dougherty SF, Ellingsworth LR (1990) Antagonistic and agonistic effects of transforming growth factor β and IL-1 in rheumatoid synovium. J Immunol 145:2514–2519Google Scholar
  44. 44.
    Dinarello CA (1991) Interleukin-1 and interleukin-1 antagonism. Blood 77:1627–1652Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • P. L. E. M. Van Lent
    • 1
  • L. A. M. Van den Bersselaar
    • 1
  • A. E. M. Holthuyzen
    • 1
  • N. Van Rooijen
    • 2
  • L. B. A. Van de Putte
    • 1
  • W. B. Van den Berg
    • 1
  1. 1.Department of RheumatologyUniversity Hospital St. RadboudNijmegenThe Netherlands
  2. 2.Department of HistologyFree UniversityAmsterdamThe Netherlands

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