Hashimoto H, Tanaka M, Suda T, Tomita T, Hayashida K, Takeuchi E, Kaneko M, Takano H, Nagata S, Ochi T
Osaka University Medical School, and Osaka Bioscience Institute, Suita, Japan.
Arthritis Rheum. 1998 Apr;41(4):657-62. doi: 10.1002/1529-0131(199804)41:4<657::AID-ART12>3.0.CO;2-N.
To investigate the expression and function of Fas ligand (FasL),which can be in a membrane-bound or soluble form, in the joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).
The concentration of soluble FasL (sFasL) in serum and synovial fluid (SF) from 24 OA and 38 RA patients was measured using an enzyme-linked immunosorbent assay. The expression of FasL on SF lymphocytes (SFL) and peripheral blood lymphocytes (PBL) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. A cytotoxic killing assay of membrane-bound FasL and purified sFasL against cultured synovial cells was also performed.
Soluble FasL was detected in the SF of patients with RA and OA, but not in their serum. The concentration of SF sFasL was remarkably higher in patients with severe RA than in patients with mild RA or with OA. RT-PCR showed that SFL, but not PBL, from RA patients expressed messenger RNA for FasL. Membrane-bound FasL induced apoptosis in cultured synovial cells from the RA and OA patients, but naturally processed human sFasL did not.
SFL from RA patients expressed FasL, and cleaved sFasL accumulated in the SF of inflamed joints. The different killing activity of membrane-bound FasL and sFasL against synovial cells may regulate Fas-mediated apoptosis in synovial cells.
研究可呈膜结合形式或可溶性形式的Fas配体（FasL）在类风湿关节炎（RA）和骨关节炎（OA）患者关节中的表达及功能。
采用酶联免疫吸附测定法检测24例OA患者和38例RA患者血清及滑液（SF）中可溶性FasL（sFasL）的浓度。通过逆转录聚合酶链反应（RT-PCR）分析评估SF淋巴细胞（SFL）和外周血淋巴细胞（PBL）上FasL的表达。还进行了膜结合FasL和纯化的sFasL对培养滑膜细胞的细胞毒性杀伤试验。
在RA和OA患者的SF中检测到可溶性FasL，但在其血清中未检测到。重度RA患者SF中sFasL的浓度显著高于轻度RA患者或OA患者。RT-PCR显示，RA患者的SFL而非PBL表达FasL信使核糖核酸。膜结合FasL可诱导RA和OA患者培养的滑膜细胞凋亡，但天然加工的人sFasL则不能。
RA患者的SFL表达FasL，且裂解的sFasL在炎症关节的SF中蓄积。膜结合FasL和sFasL对滑膜细胞的不同杀伤活性可能调节滑膜细胞中Fas介导的凋亡。
