Mazure G, Grundy J E, Nygard G, Hudson M, Khan K, Srai K, Dhillon A P, Pounder R E, Wakefield A J
Inflammatory Bowel Disease Study Group, Royal Free Hospital School of Medicine, London, U.K.
J Gen Virol. 1994 Nov;75 ( Pt 11):2863-71. doi: 10.1099/0022-1317-75-11-2863.
Measles virus infection of microvascular endothelium in vivo and ensuing endothelial cell activation may be important in the pathogenesis of subsequent inflammation in target organs. This study investigated the capacity of measles virus to induce procoagulant activity, in vitro, in endothelial cells isolated from human umbilical cord veins. Endothelial cells were infected with a clinical isolate of measles virus propagated in Vero cells. Cells were also incubated with bacterial lipopolysaccharide (10 micrograms/ml), herpes simplex virus type 1, cytomegalovirus or culture medium alone as positive and negative controls, respectively. Endothelial cell procoagulant activity was measured in a one-stage clotting assay. Measles virus stimulated both a time and dose-dependent endothelial cell procoagulant response by the induction of tissue factor synthesis, confirmed by both immunocytochemistry and its dependence on factor VII for activity. This activity was reduced by u.v.-irradiation of the virus. Infected cells were analysed by double immunofluorescent staining for both tissue factor and measles virus N-protein, and examined using confocal scanning laser microscopy. Cells expressing tissue factor were also positive for the measles virus N-protein. Low levels of interleukin-1 were detected in some viral inocula derived from measles virus-infected Vero cells, however neutralising antibody to interleukin-1 failed to inhibit the endothelial cell procoagulant response to measles virus, whereas it significantly reduced procoagulant activity induced in endothelial cells by recombinant interleukin-1. The capacity of measles virus to induce endothelial tissue factor in vitro, may be relevant to the thrombotic vasculopathy associated with measles virus infection in vivo.
麻疹病毒在体内感染微血管内皮细胞及随后引发的内皮细胞活化，可能在靶器官后续炎症的发病机制中起重要作用。本研究调查了麻疹病毒在体外对从人脐静脉分离的内皮细胞诱导促凝活性的能力。内皮细胞用在Vero细胞中繁殖的麻疹病毒临床分离株进行感染。细胞还分别与细菌脂多糖（10微克/毫升）、单纯疱疹病毒1型、巨细胞病毒或单独的培养基一起孵育作为阳性和阴性对照。在内皮细胞促凝活性的一期凝血试验中进行测定。麻疹病毒通过诱导组织因子合成刺激了内皮细胞促凝反应的时间和剂量依赖性，这通过免疫细胞化学及其对因子VII活性的依赖性得以证实。这种活性因病毒的紫外线照射而降低。通过对组织因子和麻疹病毒N蛋白进行双重免疫荧光染色对感染细胞进行分析，并使用共聚焦扫描激光显微镜进行检查。表达组织因子的细胞对麻疹病毒N蛋白也呈阳性。在一些源自麻疹病毒感染的Vero细胞的病毒接种物中检测到低水平的白细胞介素-1，然而，针对白细胞介素-1的中和抗体未能抑制内皮细胞对麻疹病毒的促凝反应，而它显著降低了重组白细胞介素-1诱导的内皮细胞促凝活性。麻疹病毒在体外诱导内皮组织因子的能力，可能与体内与麻疹病毒感染相关的血栓性血管病有关。
