Increased Expression of Phospholipid Scramblase 1 in Monocytes from Patients with Systemic Lupus Erythematosus
Increased Expression of Phospholipid Scramblase 1 in Monocytes from Patients with Systemic Lupus Erythematosus
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DOI：
10.3899/jrheum.091420
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发表时间：
2010-08
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影响因子：
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通讯作者：
E. Suzuki;O. Amengual;T. Atsumi;K. Oku;Toko Hashimoto;H. Kataoka;T. Horita;S. Yasuda;M. Ieko;K. Fukushima;T. Koike
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作者：
E. Suzuki;O. Amengual;T. Atsumi;K. Oku;Toko Hashimoto;H. Kataoka;T. Horita;S. Yasuda;M. Ieko;K. Fukushima;T. Koike
目标。据报道，系统性红斑狼疮（SLE）患者的血栓栓塞事件发生率很高。磷脂酰丝氨酸（PS）通常被隔离在细胞膜的内小叶。PS在细胞活化过程中的外化是由磷脂超燃酶1 （PLSCR1）介导的，在促进血液凝固中起着核心作用。我们通过分析SLE患者单核细胞PLSCR1的表达来研究SLE中血栓形成的潜在致病状态。方法。对60例SLE患者进行评估。23例患者有抗磷脂综合征（APS/SLE）。血浆d -二聚体水平作为纤维蛋白转换的标志。从单核细胞中提取总RNA，克隆编码人PLSCR1的cDNA，并对独立克隆进行测序。实时聚合酶链反应检测CD14+细胞PLSCR1 mRNA表达。流式细胞术分析CD14+细胞表面PS暴露情况。结果。SLE患者血浆中d -二聚体水平升高。在所有受试者中都鉴定出PLSCR1 mRNA的三个剪接变体，与健康对照组相比，SLE患者的全长PLSCR1 mRNA水平显著升高（分别为2.9±1.5 vs 1.3±0.4,p < 0.0001）。流式细胞术分析显示，与健康对照相比，SLE患者CD14+细胞表面的PS暴露相对增强。结论。发现了新的PLSCR1剪接变体。SLE患者单核细胞PLSCR1 mRNA表达增强，纤维蛋白转换和细胞表面PS暴露增加，表明PLSCR1可能在一定程度上促进了SLE的血栓形成倾向。
Objective. A high incidence of thromboembolic events has been reported in patients with systemic lupus erythematosus (SLE). Phosphatidylserine (PS) is normally sequestered in the inner leaflet of cell membranes. Externalization of PS during cell activation is mediated by phospholipid scramblase 1 (PLSCR1) and has a central role in promoting blood coagulation. We investigated the underlying pathogenic status of thrombophilia in SLE by analyzing PLSCR1 expression on monocytes from patients with SLE. Methods. Sixty patients with SLE were evaluated. Twenty-three patients had antiphospholipid syndrome (APS/SLE). Plasma D-dimer levels were measured as a marker of fibrin turnover. The cDNA encoding human PLSCR1 was cloned from the total RNA extract from monocytes, and independent clones were sequenced. PLSCR1 mRNA expression in CD14+ cells was determined by real-time polymerase chain reaction. PS exposure on CD14+ cell surface was analyzed by flow cytometry. Results. Elevated D-dimer levels were found in plasma from SLE patients. Three splice variants of PLSCR1 mRNA were identified in all subjects, and levels of full-length PLSCR1 mRNA were significantly increased in SLE compared to healthy controls (2.9 ± 1.5 vs 1.3 ± 0.4, respectively; p < 0.0001). Flow-cytometry analysis showed relative enhancement of PS exposure in the surface of CD14+ cells in SLE patients compared to healthy controls. Conclusion. Novel PLSCR1 splice variants were identified. Monocytes in SLE patients had enhanced PLSCR1 mRNA expression, as well as increased fibrin turnover and cell-surface PS exposure, indicating that PLSCR1 may, in part, contribute to the prothrombotic tendency in SLE.