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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >TLR4 is involved in the pathogenic effects observed in a murine model of antiphospholipid syndrome
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TLR4 is involved in the pathogenic effects observed in a murine model of antiphospholipid syndrome

机译：TLR4参与在抗磷脂综合征鼠模型中观察到的致病作用

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摘要

Antiphospholipid (aPL)/anti-beta 2-glycoprotein I (beta 2GPI) antibodies are considered to play a pivotal pathogenic role in antiphospholipid syndrome (APS) by inducing an intracellular signaling and procoagulant/proinflammatory phenotype that leads to thrombosis. There is increasing evidence that Toll-like receptor 4 (TLR4) could serve as an important molecule for anti-beta 2GPI recognition on target cells. However, few studies have focused on the effects of TLR4 in in vivo models. Here, we investigated the role of TLR4 in the pathogenic effects of aPL/anti-beta 2GPI more precisely using TLR4-intact (C3H/HeN) and TLR4-defective (C3H/HeJ) mice. C3H/HeN and C3H/HeJ mice were injected with either IgG isolated from patient with APS (IgG-APS) or epitope-specific anti-beta 2GPI purified from beta 2GPI peptide-immunized rabbits. We found that, following anti-beta 2GPI injections and vascular injury, thrombus formation in both the carotid artery and femoral vein was markedly reduced in C3H/HeJ mice when compared with C3H/HeN mice. IgG-APS or anti-beta 2GPI-induced carotid artery and peritoneal macrophage tissue factor activity/expression was significantly lesser in C3H/HeJ than in C3H/HeN mice. Furthermore, the IgG-APS or anti-beta 2GPI induced expression of VCAM-1, ICAM-1, and E-selectin in the aorta and of IL-1 beta, IL-6, and TNF-alpha in peritoneal macrophages of C3H/HeJ mice was also significantly reduced compared to C3H/HeN mice. Together, these data suggest that TLR4 is involved in the pathogenic effects of aPL/anti-beta 2GPI antibodies in vivo. (C) 2015 Elsevier Inc. All rights reserved.
机译：抗磷脂（aPL）/抗β2-糖蛋白I（β2GPI）抗体被认为通过诱导导致血栓形成的细胞内信号传导和促凝血/促炎表型在抗磷脂综合征（APS）中发挥关键的致病作用。越来越多的证据表明，Toll样受体4（TLR4）可以作为靶细胞上抗β2GPI识别的重要分子。但是，很少有研究集中于TLR4在体内模型中的作用。在这里，我们使用TLR4完整（C3H / HeN）和TLR4缺陷（C3H / HeJ）小鼠更精确地研究了TLR4在aPL /抗β2GPI的致病作用中的作用。向C3H / HeN和C3H / HeJ小鼠注射从APS患者中分离的IgG（IgG-APS）或从经beta 2GPI肽免疫的兔子中纯化的表位特异性抗β2GPI。我们发现，在抗β2GPI注射和血管损伤之后，与C3H / HeN小鼠相比，C3H / HeJ小鼠的颈动脉和股静脉血栓形成明显减少。 IgG-APS或抗β2GPI诱导的颈动脉和腹膜巨噬细胞组织因子的活性/表达在C3H / HeJ中明显低于C3H / HeN小鼠。此外，IgG-APS或抗beta 2GPI诱导主动脉中VCAM-1，ICAM-1和E-选择素的表达以及C3H /腹膜巨噬细胞中IL-1 beta，IL-6和TNF-α的表达。与C3H / HeN小鼠相比，HeJ小鼠也明显减少。总之，这些数据表明TLR4参与了aPL /抗β2GPI抗体的体内致病作用。 （C）2015 Elsevier Inc.保留所有权利。

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