Dimitriu-Bona A, Matic M, Ding W, Yang C P, Fillit H
Henry L. Schwartz Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, New York 10029-6574, USA.
Clin Immunol Immunopathol. 1995 Sep;76(3 Pt 1):234-40. doi: 10.1006/clin.1995.1121.
Vasculitis is an common clinical feature of systemic lupus erythematosus (SLE) in humans and in animal models of this disease. Humoral autoimmunity against endothelial cells has been previously demonstrated in SLE and other autoimmune disorders, but the precise cell surface antigenic targets involved in the initiation and progression of vascular injury are still essentially unknown. In the current studies, we demonstrate the presence of autoantibodies in the sera of MRL/lpr/lpr mice which bind endothelial cell surface antigens by ELISA and also cause complement-dependent cytotoxicity of these cells. These MRL/lpr/lpr sera induced complement-dependent cleavage and release of 35SO4-labeled material containing primarily cell surface heparan sulfate proteoglycans from these cells, and react with heparin (a glycosaminoglycan related to heparan sulfate) by ELISA and liquid-phase competitive inhibition ELISA. These data indicate that antiendothelial cell autoantibodies present in autoimmune MRL/lpr/lpr mice are directed at least in part against cell surface heparan sulfate proteoglycans. Autoantibodies to cell surface heparan sulfate proteoglycan may play a role in vascular endothelial cell injury in these animals through complement-dependent, autoimmune mechanisms.
血管炎是人类系统性红斑狼疮（SLE）以及该疾病动物模型的常见临床特征。先前已在SLE和其他自身免疫性疾病中证实了针对内皮细胞的体液自身免疫，但血管损伤起始和进展过程中涉及的确切细胞表面抗原靶点仍基本未知。在当前研究中，我们通过ELISA证明MRL/lpr/lpr小鼠血清中存在结合内皮细胞表面抗原的自身抗体，并且这些自身抗体还会导致这些细胞发生补体依赖性细胞毒性。这些MRL/lpr/lpr血清诱导补体依赖性裂解并释放主要含有细胞表面硫酸乙酰肝素蛋白聚糖的35SO4标记物质，并且通过ELISA和液相竞争抑制ELISA与肝素（一种与硫酸乙酰肝素相关的糖胺聚糖）发生反应。这些数据表明，自身免疫性MRL/lpr/lpr小鼠中存在的抗内皮细胞自身抗体至少部分针对细胞表面硫酸乙酰肝素蛋白聚糖。针对细胞表面硫酸乙酰肝素蛋白聚糖的自身抗体可能通过补体依赖性自身免疫机制在这些动物的血管内皮细胞损伤中发挥作用。
