Cines D B, Lyss A P, Reeber M, Bina M, DeHoratius R J
J Clin Invest. 1984 Mar;73(3):611-25. doi: 10.1172/JCI111251.
Vasculitis in systemic lupus erythematosus (SLE) is associated with the deposition of IgG and complement in blood vessel walls. However, it is not known whether immune injury to endothelial cells is a part of this process. Therefore, we used a solid phase radioimmunoassay to study the ability of IgG from normal human sera and sera from patients with SLE to bind to endothelial cells. In this assay, cultured human umbilical venous endothelial cells were sequentially incubated with normal or SLE sera, goat anti-human IgG, and 125I-labeled staphylococcal protein A (*SPA). After exposure to normal sera, 2.5 +/- 0.5% (mean +/- SD) of the added *SPA bound to the cells, whereas after exposure to SLE sera 13.8 +/- 7.6% of the added *SPA bound to these cells. This difference in binding was highly significant (P less than 0.001). Binding was partially reduced when SLE sera were preincubated with B-lymphocytes or monocytes, but not after exposure to erythrocytes, platelets, or T lymphocytes. Incubation of endothelial cells with the 7S fraction of SLE sera or with the F(ab')2 fragment of SLE-IgG resulted in the deposition of greater than 80% as much IgG as was deposited on endothelial cells by whole serum. However, since higher molecular weight fractions (greater than 7S) of SLE sera were also active, we tested the capacity of endothelial cells to bind IgG complexes. Endothelial cells bound heat-aggregated IgG (HA-IgG) in a saturable manner at one log concentration below the binding of normal monomeric IgG. Binding of HA-IgG to endothelial cells was markedly enhanced by preincubation with a serum source of complement. Both HA-IgG and SLE-IgG also bound to freshly obtained endothelial cells in suspension, as detected by automated fluorescence flow cytometry. Binding of SLE-IgG and HA-IgG to endothelium initiated complement activation, deposition of the third component of complement, and disruption of the monolayer. In addition, SLE-IgG and HA-IgG caused endothelial cells to secrete prostacyclin and caused the adherence of platelets, confirmed by scanning electron microscopy. These studies demonstrate that IgG anti-endothelial antibodies are present in the sera of patients with active SLE. These sera may also contain IgG complexes that are capable of binding to endothelial cells. The association of IgG and complement with endothelial cells may initiate vascular injury in SLE and other human disorders.
系统性红斑狼疮（SLE）中的血管炎与免疫球蛋白G（IgG）和补体在血管壁中的沉积有关。然而，尚不清楚内皮细胞的免疫损伤是否是这一过程的一部分。因此，我们使用固相放射免疫测定法研究正常人血清和SLE患者血清中的IgG与内皮细胞结合的能力。在该测定中，将培养的人脐静脉内皮细胞依次与正常或SLE血清、山羊抗人IgG和125I标记的葡萄球菌蛋白A（SPA）孵育。暴露于正常血清后，添加的SPA中有2.5±0.5%（平均值±标准差）与细胞结合，而暴露于SLE血清后，添加的*SPA中有13.8±7.6%与这些细胞结合。这种结合差异具有高度显著性（P小于0.001）。当SLE血清与B淋巴细胞或单核细胞预孵育时，结合部分减少，但暴露于红细胞、血小板或T淋巴细胞后则没有减少。用SLE血清的7S组分或SLE-IgG的F(ab')2片段孵育内皮细胞，导致沉积的IgG量大于全血清在内皮细胞上沉积量的80%。然而，由于SLE血清的高分子量组分（大于7S）也具有活性，我们测试了内皮细胞结合IgG复合物的能力。内皮细胞以饱和方式结合热聚集IgG（HA-IgG），其浓度比正常单体IgG的结合浓度低一个对数。用补体血清源预孵育可显著增强HA-IgG与内皮细胞的结合。通过自动荧光流式细胞术检测，HA-IgG和SLE-IgG也与新鲜获得的悬浮内皮细胞结合。SLE-IgG和HA-IgG与内皮的结合引发补体激活、补体第三成分的沉积以及单层的破坏。此外，SLE-IgG和HA-IgG导致内皮细胞分泌前列环素，并导致血小板黏附，扫描电子显微镜证实了这一点。这些研究表明，活动性SLE患者血清中存在抗内皮细胞IgG抗体。这些血清中可能还含有能够与内皮细胞结合的IgG复合物。IgG和补体与内皮细胞的关联可能引发SLE和其他人类疾病中的血管损伤。
