Slobodin Gleb, Pavlotzky Elsa, Panov Julia, Rosner Itzhak, Kessel Aharon, Toubi Elias
Department of Internal Medicine, Bnai Zion Medical Center and Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Immunol Invest. 2008;37(8):841-8. doi: 10.1080/08820130802438016.
Systemic sclerosis (SSc) is characterized by both vasculopathy and autoimmunity. The interplay between these pathogenetic links requires further exploration. The aim was to assess the interrelationship of endothelin-1 (ET-1), a vasoconstrictor peptide, whose levels are usually elevated in the plasma of the patients with SSc and the function of monocyte-derived dendritic cells (MDDCs), which serve as organizers of the immune response. MDDCs were grown from 5 patients with SSc and severe Raynaud's phenomenon and 5 healthy volunteers. The cells were further stimulated by synthetic ET-1, lipopolysaccharide (LPS) or both. The production of endogenous ET-1, TNFalpha and IL-12 was assessed by RT-PCR and/or ELISA. The plasma levels of ET-1 were significantly higher in patients with SSc compared to healthy controls (p = 0.0005). The production of ET-1 by MDDCs was negligible in all examined conditions, while the release of TNFalpha and IL-12 was stimulated by LPS but not by ET-1. The in vitro concentration of the exogenous ET-1, where added, was comparable to the plasma levels of ET-1 in patients with SSc. High plasma levels of ET-1 are characteristic for the patients with SSc and severe Raynaud's phenomenon. An in vitro model with concentrations of ET-1 comparable to those in the plasma of SSc patients has been elaborated. The examined function of MDDCs from SSc patients and healthy volunteers did not differ under these conditions and was not dependent on the presence of ET-1.
系统性硬化症（SSc）的特征在于血管病变和自身免疫。这些致病环节之间的相互作用需要进一步探索。目的是评估内皮素-1（ET-1）（一种血管收缩肽，其水平在SSc患者血浆中通常升高）与单核细胞衍生树突状细胞（MDDC）的功能之间的相互关系，MDDC作为免疫反应的组织者。从5例患有SSc和严重雷诺现象的患者以及5名健康志愿者中培养MDDC。细胞进一步用合成ET-1、脂多糖（LPS）或两者进行刺激。通过逆转录聚合酶链反应（RT-PCR）和/或酶联免疫吸附测定（ELISA）评估内源性ET-1、肿瘤坏死因子α（TNFα）和白细胞介素-12（IL-12）的产生。与健康对照相比，SSc患者血浆中ET-1水平显著更高（p = 0.0005）。在所有检测条件下，MDDC产生ET-1的量可忽略不计，而TNFα和IL-12的释放受到LPS刺激，但不受ET-1刺激。添加的外源性ET-1的体外浓度与SSc患者血浆中ET-1水平相当。高血浆ET-1水平是患有SSc和严重雷诺现象患者的特征。已经构建了一种体外模型，其中ET-1浓度与SSc患者血浆中的浓度相当。在这些条件下，来自SSc患者和健康志愿者的MDDC的检测功能没有差异，并且不依赖于ET-1的存在。
