Phagocytic synovial lining cells regulate acute and chronic joint inflammation after antigenic exacerbation of smouldering experimental murine arthritis

Abstract

Objective: To investigate the in vivo role of phagocytic synovial lining cells in inflammation after exacerbation of smouldering murine antigen induced arthritis.

Methods: Phagocytic synovial lining cells were selectively depleted, by intraarticular injection of clodronate laden liposomes, 2 weeks after induction of modified bovine serum albumin induced arthritis. Exacerbation of arthritis was induced at Week 3, intravenously or locally into the knee joint. Arthritis was evaluated by 99mTc uptake measurements or in hematoxylin and eosin stained sections. Retention of radiolabeled antigen was evaluated by external measurement of radioactivity or autoradiography. Chemotactic factor production and interleukin 1 (IL-1) protein level were detected in washout samples of arthritic joints by transwell chemotactic assay and NOB.EL-4 bioassay or immunolocalization, respectively.

Results: One day after induction of flare, swelling measured by 99mTc uptake was similar in control and lining depleted knee joints. Histological examination of control reactivated knee joints revealed infiltrate in both superficial and deep synovial layers, while florid exudate occurred in the joint cavity. In lining depleted reactivated knee joints infiltrate was significantly decreased, found mainly in the deep synovial layer around the blood vessels, whereas exudate was significantly lower. No difference was found in the topography of the synovial infiltrate for antigen given intraarticularly versus intravenously. Antigen removal was slowed in lining depleted joints and autoradiographs showed antigen persistence mainly in the joint cavity and the synovial layer. Reduced influx of inflammatory cells was correlated to decreased production of chemotactic factors. Level of IL-1 was lower in washouts and was mainly detected in macrophages in the deep layer, as shown by immunolocalization. In controls, more IL-1 was detected in the lining and subsynovial layer. At Day 7 after exacerbation no synovitis was found in the synovial lining cell depleted arthritic joint, whereas florid synovitis persisted in the arthritic control joint.

Conclusion: Phagocytic synovial lining cells are involved in acute and chronic inflammation after exacerbation of hyperreactive joints with antigen given either directly into the knee joint or intravenously.