THE APOPTOSIS-1 FAS PROTEIN IN HUMAN SYSTEMIC LUPUS-ERYTHEMATOSUS
THE APOPTOSIS-1 FAS PROTEIN IN HUMAN SYSTEMIC LUPUS-ERYTHEMATOSUS
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DOI：
10.1172/jci117051
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发表时间：
1994-03-01
影响因子：
15.9
通讯作者：
ELKON, KB
中科院分区：
文献类型：
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作者：
MYSLER, E;BINI, P;ELKON, KB
三个独立的突变涉及凋亡-1（APO-1）/Fas受体或其假定的配体导致狼疮样疾病与淋巴结病在不同品系的小鼠。为了确定SLE患者是否也存在这种凋亡途径的缺陷，我们使用流式细胞术和单克隆抗体抗APO-1分析了新鲜分离的血液单核细胞和体外活化的淋巴细胞上APO-1的表达。狼疮患者外周血B细胞和CD 4+、CD 8 + T淋巴细胞的载脂蛋白O-1表达水平明显高于正常对照组（P < 0.001）。几乎90%的APO-1染色阳性的细胞也表达CD 29抗原，表明APO-1在体内淋巴细胞活化后上调。在IL-2存在下，在体外激活SLE T（抗CD 3）或B（金黄色葡萄球菌科万1）淋巴细胞后，未检测到载脂蛋白-1调节缺陷。同样，抗APO-1抗体在体外诱导74+/-5%活化的SLE T细胞凋亡，而正常对照组为79+/-6%（P > 0.05）。这些结果表明，虽然APO-1/Fas可能在SLE淋巴细胞存活的调节中发挥重要作用，但在这些研究中未检测到该受体表达或功能的一致缺陷。
Three independent mutations involving the apoptosis-1 (APO-1)/Fas receptor or its putative ligand have led to lupuslike diseases associated with lymphadenopathy in different strains of mice. To determine whether humans with SLE also have a defect in this apoptosis pathway, we analyzed the expression of APO-1 on freshly isolated blood mononuclear cells and on lymphocytes activated in vitro using flow cytometry and the monoclonal antibody anti-APO-1. Significantly higher levels of APO-1 expression were detected on freshly isolated peripheral B cells and both CD4(+) and CD8(+) T lymphocyte populations obtained from lupus patients when compared with normal controls (P < 0.001). Almost 90% of the cells that stained positive for APO-1 also expressed the CD29 antigen, suggesting that APO-1 was upregulated after lymphocyte activation in vivo. No defect in APO-1 regulation was detected after activation of SLE T (with anti-CD3) or B (with Staphylococcus aureus Cowan 1) lymphocytes in the presence of IL-2 in vitro. Similarly, the anti-APO-1 antibody induced apoptosis in 74+/-5% of activated SLE T cells in vitro compared with 79+/-6% of the normal controls (P > 0.05). These results reveal that, while APO-1/Fas may play an important role in the regulation of lymphocyte survival in SLE, no consistent defect in the expression or function of the receptor could be detected in these studies.