Ronday H K, van der Laan W H, Tak P P, de Roos J A, Bank R A, TeKoppele J M, Froelich C J, Hack C E, Hogendoorn P C, Breedveld F C, Verheijen J H
Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands.
Rheumatology (Oxford). 2001 Jan;40(1):55-61. doi: 10.1093/rheumatology/40.1.55.
To investigate the cartilage-degrading capacity of granzyme B and the presence of granzyme B-positive cells at sites of erosion in the rheumatoid synovium.
Granzyme B was added to [(3)H]proline/[(35)S]sulphate-labelled cartilage matrices and to cartilage explants. Proteoglycan degradation was assessed by the release of (35)S and glycosaminoglycans into the medium and collagen degradation was assessed by the release of (3)H and hydroxyproline and by measuring the fraction of denatured collagen. Granzyme B expression was studied at the invasive front of the synovium by immunohistochemistry.
Granzyme B induced loss of both newly synthesized, radiolabelled proteoglycans in cartilage matrices and resident proteoglycans of the cartilage explants. No effect on collagen degradation was found. Granzyme B-positive cells were present throughout the synovium and at the invasive front.
The presence of granzyme B-positive cells at the invasive front of the synovium together with its ability to degrade articular proteoglycans supports the view that granzyme B may contribute to joint destruction in rheumatoid arthritis.
研究颗粒酶B降解软骨的能力以及类风湿性滑膜炎糜烂部位颗粒酶B阳性细胞的存在情况。
将颗粒酶B添加到[³H]脯氨酸/[³⁵S]硫酸盐标记的软骨基质和软骨外植体中。通过³⁵S和糖胺聚糖释放到培养基中来评估蛋白聚糖的降解，通过³H和羟脯氨酸的释放以及测量变性胶原蛋白的比例来评估胶原蛋白的降解。通过免疫组织化学研究颗粒酶B在滑膜侵袭前沿的表达。
颗粒酶B导致软骨基质中新合成的放射性标记蛋白聚糖以及软骨外植体中的驻留蛋白聚糖均减少。未发现对胶原蛋白降解有影响。颗粒酶B阳性细胞存在于整个滑膜以及侵袭前沿。
滑膜侵袭前沿存在颗粒酶B阳性细胞及其降解关节蛋白聚糖的能力支持了颗粒酶B可能导致类风湿性关节炎关节破坏的观点。
