Bengtsson Anders A, Gullstrand Birgitta, Truedsson Lennart, Sturfelt Gunnar
Department of Rheumatology, Lund University Hospital, SE-221 85, Lund, Sweden.
Clin Immunol. 2008 Jan;126(1):57-66. doi: 10.1016/j.clim.2007.10.003. Epub 2007 Nov 26.
The main source of autoantigens in systemic lupus erythematosus (SLE) is most likely apoptotic material. We have previously shown that sera from SLE patients can induce apoptosis in monocytes and lymphocytes, and here we characterized mechanisms of apoptosis induced by SLE serum. SLE serum seems to induce caspase-dependent classical apoptosis since cells exposed to SLE serum displayed morphology consistent with classical apoptosis as demonstrated by confocal microscopy, and pan-caspase inhibitor Z-VAD.fmk significantly reduced SLE serum-induced apoptosis. Death-receptor-independent pathways seemed to be involved since SLE serum induced apoptosis equally in FADD-mutant and wild-type Jurkat cell lines, and blocking of Fas and TNFR1 did not reduce apoptosis induction. Importantly, apoptosis was significantly reduced in a Bcl-2 overexpressing Jurkat cell line indicating involvement of mitochondrial pathways. Thus, based on morphology and caspase inhibition experiments, we have demonstrated that SLE serum induce classical caspase-dependent apoptosis, and this was independent of death receptor pathways.
系统性红斑狼疮（SLE）中自身抗原的主要来源很可能是凋亡物质。我们之前已经表明，SLE患者的血清可诱导单核细胞和淋巴细胞凋亡，在此我们对SLE血清诱导凋亡的机制进行了表征。SLE血清似乎诱导依赖半胱天冬酶的经典凋亡，因为通过共聚焦显微镜观察，暴露于SLE血清的细胞呈现出与经典凋亡一致的形态，并且泛半胱天冬酶抑制剂Z-VAD.fmk显著降低了SLE血清诱导的凋亡。由于SLE血清在FADD突变型和野生型Jurkat细胞系中诱导凋亡的程度相同，且阻断Fas和TNFR1并未降低凋亡诱导，因此似乎涉及死亡受体非依赖性途径。重要的是，在过表达Bcl-2的Jurkat细胞系中凋亡显著减少，表明线粒体途径参与其中。因此，基于形态学和半胱天冬酶抑制实验，我们证明了SLE血清诱导经典的依赖半胱天冬酶的凋亡，且这与死亡受体途径无关。
