IgG antiendothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro - Induction of adhesion molecule expression and involvement of endothelium-derived cytokines
IgG antiendothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro - Induction of adhesion molecule expression and involvement of endothelium-derived cytokines
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DOI：
10.1172/jci118377
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发表时间：
1996-01-01
影响因子：
15.9
通讯作者：
Pearson, JD
中科院分区：
文献类型：
--
作者：
Carvalho, D;Savage, COS;Pearson, JD
通过 ELISA 在硬皮病患者的 42 份血清样本中的 30 份中检测到了结合人内皮细胞 (AECA) 的 IgG 自身抗体。用AECA阳性硬皮病血清或从这些血清中纯化的IgG预处理人脐静脉内皮细胞，导致细胞结合人U937单核细胞的能力呈剂量和时间依赖性增加。阈值活性IgG浓度为1-10μg/ml； 3小时后效果显着，6-12小时后效果最大。来自AECA阴性血清或正常血清的IgG没有效果。 U937细胞粘附力的增加伴随着内皮细胞间粘附分子-1、血管细胞粘附分子-1和E-选择素表达的增加。用 AECA 预处理和 IgG 免疫耗竭后内皮细胞条件培养基的转移证明存在模拟 AECA 作用的可转移活性。用中和性抗细胞因子抗体处理表明内皮细胞响应AECA产生的IL-1参与粘附分子和U937细胞粘附的上调。我们得出结论，AECA 可以通过激活内皮细胞在硬皮病中发挥致病作用，部分原因是 IL-1 的自分泌或旁分泌作用。
IgG autoantibodies that bind human endothelial cells (AECA) were detected by ELISA in 30 of 42 samples of sera from patients with scleroderma. Pretreatment of human umbilical vein endothelial cells with AECA-positive scleroderma sera, or IgG purified from these sera, led to a dose- and time-dependent increase in the ability of the cells to bind human U937 monocytic cells. Threshold-active IgG concentrations were 1-10 mu g/ml; effects were significant after 3 h and maximal after 6-12 h. IgG from AECA-negative sera or normal sera were without effect. Increased adhesion of U937 cells was accompanied by increased expression of endothelial intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Transfer of endothelial cell-conditioned media after pretreatment with AECA and immunodepletion of IgG demonstrated the presence of transferable activity that mimicked the effects of AECA. Treatment with neutralizing anticytokine antibodies indicated that IL-I, generated by the endothelial cells in response to AECA, was involved in the upregulation of adhesion molecules and U937 cell adhesion. We conclude that AECA can play a pathogenic role in scleroderma by activating endothelial cells, in part due to autocrine or paracrine actions of IL-1.