Functional heterogeneity of anti-endothelial cell antibodies
Functional heterogeneity of anti-endothelial cell antibodies
复制标题
DOI：
10.1046/j.1365-2249.2001.01528.x
复制
发表时间：
2001-06-01
影响因子：
4.6
通讯作者：
Youinou, P
中科院分区：
文献类型：
--
作者：
Bordron, A;Révélen, R;Youinou, P
虽然有人声称，一些抗内皮细胞抗体（AECA）激活EC，也有证据表明，其他触发细胞凋亡。为了解决活化是否是AECA介导的EC凋亡的先决条件的问题，评价了23个AECA阳性血清诱导活化和/或凋亡的能力。活化被定义为E-选择素和细胞间粘附分子1的过度表达。光学显微镜，膜联蛋白V结合，亚倍体细胞计数，并测定聚（ADP-核糖）聚合酶裂解相关产物被用来评估细胞凋亡。定义了四种功能谱：10种血清促进活化和凋亡（act+/apo+），1种为act+/apo-，6种为act-/apo+，其余6种为act-/apo-。血栓调节蛋白的膜表达减少与细胞凋亡有关，而不是活化。Caspase-3参与了两种凋亡模型，几种存活蛋白与Bax的比率降低，而不管apo+ AECA激活细胞的能力如何，而自由基氧似乎不参与。此外，巨噬细胞吞噬用促凋亡AECA处理的EC，但不吞噬用不诱导凋亡的AECA孵育的EC。因此，AECA代表了一个极其异质性的自身抗体家族，这不仅是因为其靶抗原的多样性，而且还因为其效应的后续多样性。
While it has been claimed that some anti-endothelial cell antibodies (AECA) activate EC, there is also evidence that others trigger apoptosis. To address the issue of whether activation is a prerequisite for AECA-mediated apoptosis of EC, 23 AECA-positive sera were evaluated for their ability to induce activation and/or apoptosis. Activation was defined as an over-expression of E-selectin and intercellular adhesion molecule 1. Optical microscopy, annexin V binding, hypoploid cell enumeration, and determination of poly (ADP-ribose) polymerase cleavage-related products were used to assess apoptosis. Four functional profiles were defined: 10 sera promoted activation and apoptosis (act+/apo+), one was act+/apo-, six act-/apo+, and the remaining six act-/apo-. The reduced membrane expression of thrombomodulin was associated with apoptosis, rather than activation. Caspase-3 was implicated in the two models of apoptosis, the ratios of several survival proteins to Bax decreased, regardless of the ability of apo+ AECA to activate the cells, while radical oxygen species did not appear to be involved. Furthermore, it occurred that macrophages engulfed EC treated with apoptosis-promoting AECA, but not those incubated with AECA that did not induce apoptosis. Hence, AECA represent an extremely heterogeneous family of autoantibodies, not only because of the variety of their target antigens, but also the subsequent diversity of their effects.