Immunolocalization of bradykinin receptors on human synovial tissue
Introduction
The degree of inflammation and joint destruction vary in the different arthritides. This may be due to a difference in the initiating factors and/or pathogenesis. Rheumatoid arthritis is characterized by infiltration of synovial membrane by monocytes and plasma cells, an influx of neutrophils into the synovial fluid and progressive joint damage with bone resorption and erosions. In osteoarthritis, the articular cartilage is primarily affected with disruption of the collagen network due to a change in the balance of proteolytic enzymes and their inhibitors. In avascular necrosis there is necrosis of bone due to an interruption in the blood supply.
The kallikrein–kinin system has been implicated in the pathogenesis of experimental and clinical inflammatory joint disease (Bhoola et al., 1992). Both tissue and plasma kallikrein have been identified in joint effusions in RA and OA and higher enzyme activity together with raised kinin levels have been reported in RA as compared to OA (Rahman et al., 1994; Rahman et al., 1995). In addition, we have previously demonstrated a loss of the kinin moiety on circulating and synovial fluid neutrophils and an increased signal from kinin B2 receptors on synovial fluid neutrophils in RA (Cassim et al., 1996). Besides their proinflammatory properties, kinins have also been shown to increase bone resorption in vitro via the formation of prostaglandins (Lerner, 1994).
Bradykinin binding sites have been localized on human synovial tissue by Scatchard analysis (Uhl et al., 1992) and by autoradiographic localization (Bathon et al., 1992). The kinin B2 receptor was present in higher density in RA than in OA and treatment with interleukin-1 enhanced the number of binding sites (Bathon et al., 1992). The ability of kinins to stimulate bone resorption in vitro and the presence of bradykinin receptors on synovial tissue suggests that kinins may regulate bone destruction in inflammatory arthritis. The aim of this study was to demonstrate immunohistochemically kinin B1 and B2 receptors in human synovial tissue.
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Patients
Synovial tissue was obtained from the hip and knee joints at the time of joint replacement surgery or arthroscopic synovectomy. Six patients were admitted into the study, two with OA, two with avascular necrosis of the hip and two with RA. Of the two patients with RA one underwent joint replacement surgery for chronic arthritis and the second patient had active inflammation at the time of synovial biopsy.
Sample collection
The synovial tissue was dissected free from surrounding tissues, thoroughly washed with
Results
Structural detail of the synovial tissue was demonstrated on H and E staining (Fig. 1a). The image processing programme of the confocal microscope was used to record the fluorescence emitted from the CY3-labelled secondary antibody linked to the primary antibody with pseudocolour gradients on confocal microscopy. On light microscopy the brown immuno-precipitate formed by diaminobenzidine was used to detect specific staining.
The kinin B2 receptor was immunovisualized on the synovial lining cells
Discussion
Kinins are thought to be key mediators in inflammatory joint disease. The cellular and physiological actions of kinins are mediated through the activation of bradykinin receptors. Two types of bradykinin receptors have been identified, B1 and B2. While the B2 receptor is constitutive, the B1 receptor is induced in inflammation. Previous studies have identified a single bradykinin binding site of kinin B2 specificity on human synovial tissue by autoradiographic localization and Scatchard
Acknowledgements
We thank F. Hess and W. Müller-Esterl for kindly donating B1 and B2 antibodies, respectively. We also thank Mrs. C. Snyman and the Foundation for Research and Development, South Africa for their assistance with confocal microscopy.
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