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


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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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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