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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated thein vivo role of phagocytic synovial lining cells (SLC) in sustaining synovial inflammation during chronic arthritis and their function in exacerbation of smouldering synovitis in the mouse. Phagocytic SLC were depleted by a single injection of multilamellar liposomes containing the drug dichloromethylene diphosphonate (clodronate). Liposomes are preferentially taken up by macrophages and the drug is released within the cell in large amounts. Within a few days macrophages are removed from the joint. A single injection of clodronate liposomes given into the knee joint, 7 days after induction of antigen-induced (mBSA) arthritis stripped the thickened lining for the greater part. Optimal elimination was observed 7 days after liposome injection. No recovery of the synovitis was observed there-after. In addition reactivation of synovitis was induced by giving 350 μg mBSA intravenously. In SLC depleted arthritic knee joints, a significant decrease in flare was observed if compared to control, PBS injected arthritic knee joints. IL-1 levels which are elevated 6 h after induction of the flare were also significantly reduced in SLC depleted arthritic joints. Our data indicate that phagocytic SLC are directly involved in propagation and exacerbation of chronic synovitis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1437-160X
    Keywords: Arthritis ; Dichloromethylene diphosphonate ; Synovial lining cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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