IN-VIVO ROLE OF PHAGOCYTIC SYNOVIAL LINING CELLS IN ONSET OF EXPERIMENTAL ARTHRITIS

The in vivo role of phagocytic synovial lining cells (SLC) was studied in acute experimental arthritis in the mouse. SLCs were selectively d epleted by injecting liposomes encapsulating the drug dichloromthylene diphosphonate (CL2MDP, Clodronate). Optimal depletion of phagocytic l ining cells occurred 7 days after CL2MDP liposome injection. Eliciting an immune complex-mediated arthritis in SLC-depleted knee joints larg ely prevented inflammation if compared to control arthritic knee joint s. Joint swelling and influx of inflammatory cells into the joint cavi ty was markedly diminished. Cartilage damage, in this model related to influx of inflammatory cells, was significantly decreased. Reduced in flux of inflammatory cells (mainly polymorphonuclear neutrophils) was correlated to a decreased production of chemotactic factors as measure d in washouts of arthritic joints in a two-compartment Transwell syste m. Interleukin-1-driven chemotactic factors seem to be involved. Inter leukin-1 levels were significantly lowered in SLC-depleted arthritic k nee joints as compared to controls. Injection of recombinant murine in terleukin-1 in SLC-depleted knee joints caused less influx of inflamma tory cells as compared to injection into control knee joints. A specif ic damage of CL2MDP liposome treatment to synovial blood vessels was e xcluded as intraarticular injection of human recombinant C5a in lining -depleted knee joints showed similar influx of inflammatory cells if c ompared to human recombinant C5a injection in control knee joints. Thi s study indicates that in immune complex-mediated arthritis, phagocyti c lining cells regulate the onset of the inflammatory response.