Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells
Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells
复制标题
DOI：
10.1016/j.thromres.2011.11.048
复制
发表时间：
2012-10-01
影响因子：
7.5
通讯作者：
Ichihara, Kiyoshi
中科院分区：
文献类型：
--
作者：
Motoki, Yukari;Nojima, Junzo;Ichihara, Kiyoshi
在系统性红斑狼疮（SLE）患者中，动脉硬化闭塞症（ASO）的患病率很高，尽管缺乏ASO的常见危险因素。本研究的主要目的是探讨在SLE患者中经常检测到的抗磷脂抗体（apl）在ASO发病机制中的可能直接作用。材料与方法：用流式细胞术检测了89例伴有或不伴有ASO和/或apl的SLE患者单核细胞表面组织因子（TF）的表达，并研究了SLE患者或正常健康志愿者血浆纯化IgG (apl + IgG, n = 8；apl (-) IgG, n = 6；正常IgG， n = 6)对健康外周血单核细胞（PBMCs）或分离的单核细胞中TF表达及tnf - α和IL-1 β产生的影响。结果：我们证实单核细胞TF的高表达与ASO的患病率和apl的存在密切相关。用apl (-) IgG或正常IgG处理PBMCs时，TF、tnf - α和IL-1 β信使RNA （mRNA）的表达以及tnf - α和IL-1 β的产生均未显著增加。然而，用apl (+) IgG刺激PBMCs可显著增加TF、tnf - α和IL-1 β mRNA的表达。此外，apl (+) IgG刺激PBMCs，显著提高tnf - α和IL-1 β的产生。结论：这些结果提示igg - apl通过与外周血单核细胞和淋巴细胞相互作用导致TF持续高表达和炎性细胞因子的产生，这可能是SLE患者特有ASO发病的重要机制。(c) 2011 Elsevier Ltd.版权所有。
Introduction: In systemic lupus erythematosus (SLE) patients, the prevalence of arteriosclerosis obliterans (ASO) is high despite a lack of common risk factors for ASO. The main objective of this study was to investigate a possible direct role of anti-phospholipid antibodies (aPLs), which are frequently detected in SLE patients, in the pathogenesis of ASO.Materials and Methods: We examined tissue factor (TF) expression on the monocyte surface by flow cytometric analysis in 89 SLE patients with or without ASO and/or aPLs and studied the in vitro effect of purified IgG fractions from plasma of SLE patients or normal healthy volunteers (aPLs(+) IgG, n = 8; aPLs(-) IgG, n = 6; Normal IgG, n = 6) on the expression of TF and production of TNF-alpha and IL-1 beta in healthy peripheral blood mononuclear cells (PBMCs) or isolated monocytes.Results: We confirmed that high expression of monocyte TF was strongly associated with the prevalence of ASO and the presence of aPLs. Treatments of PBMCs with aPLs(-) IgG or normal IgG did not significantly increase expression of TF, TNF-alpha, and IL-1 beta messenger RNA (mRNA) and the production of TNF-alpha and IL-1 beta. However, stimulation of PBMCs with aPLs(+) IgG caused significant increase in expression of TF, TNF-alpha, and IL-1 beta mRNA. Moreover, aPLs(+) IgG stimulated PBMCs and significantly enhanced the production of TNF-alpha and IL-1 beta.Conclusion: These results suggest that IgG-aPLs cause persistently high TF expression and inflammatory cytokine production by interacting with peripheral blood monocytes and lymphocytes, which may be an important mechanism in the pathogenesis of ASO peculiar to SLE patients. (c) 2011 Elsevier Ltd. All rights reserved.