Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro: two procoagulant activities are produced by peripheral blood mononuclear cells.
Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro: two procoagulant activities are produced by peripheral blood mononuclear cells.
复制标题
DOI：
10.1172/jci110201
复制
发表时间：
1981-06
期刊：
影响因子：
--
通讯作者：
B. Schwartz;G. Levy;L. Curtiss;D. Fair;T. Edgington
中科院分区：
文献类型：
--
作者：
B. Schwartz;G. Levy;L. Curtiss;D. Fair;T. Edgington
在分析脂蛋白对淋巴细胞功能的影响的过程中，观察到生理浓度的分离的人血浆脂蛋白具有不同的能力，以快速增强体外人外周血单核细胞的促凝活性的表达。在一个严格的剂量依赖性的方式，极低密度脂蛋白，中密度脂蛋白，和高密度脂蛋白增强的表面表达的活细胞和总细胞内容物的促凝血活性在6小时的孵育。极低密度脂蛋白诱导凝血活酶活性表达最大增加6.7倍，这与组织因子一致，因为它依赖于因子VII、X和II。中密度脂蛋白和高密度脂蛋白诱导不同的促凝血活性增加约12倍，这似乎是一种直接的凝血酶原激活剂。该凝血酶原酶是钙依赖性的，并被2.5 mM二异丙基氟磷酸盐抑制，但不被抗因子X抗体或因子Xa抑制剂中和。与其他脂蛋白密度类别相反，低密度脂蛋白不刺激促凝血活性，而是积极抑制刺激性脂蛋白诱导的两种促凝血活性的产生。低密度脂蛋白的抑制作用在低密度脂蛋白与刺激性脂蛋白的摩尔比为1：3或更低时是明显的。由于低密度脂蛋白的抑制作用，所有脂蛋白的重组到生理浓度并不具有刺激性。这些数据表明，分离的血浆脂蛋白能够调节两种不同的促凝血活性的外周血单核细胞在体外的表达。这些相互作用可能与某些类型的高脂蛋白血症和血栓栓塞性疾病之间的联系有关，值得研究。
In the process of analyzing the effects of lipoproteins on functions of lymphoid cells, it was observed that physiological concentrations of isolated human plasma lipoproteins possess varying capacities to rapidly enhance the expression of procoagulant activity of human peripheral blood mononuclear cells in vitro. In a strict dose-dependent fashion, very low density lipoprotein, intermediate density lipoprotein, and high density lipoprotein enhanced both the surface expression by viable cells and the total cellular content of procoagulant activity during a 6-h incubation. Very low density lipoprotein induced a maximal 6.7-fold increase in the expression of a thromboplastin activity, which was consistent with tissue factor, in that it was dependent on Factors VII, X, and II. Both intermediate density lipoprotein and high density lipoprotein induced approximately a 12-fold increase of a different procoagulant activity which appears to be a direct prothrombin activator. This prothrombinase was calcium dependent and was inhibited by 2.5 mM diisopropylfluorophosphate, but was not neutralized by anti-Factor X antibodies or by inhibitors of Factor Xa. In contrast to the other lipoprotein density classes, low density lipoprotein did not stimulate procoagulant activity, but instead actively suppressed the generation of the two procoagulant activities induced by the stimulatory lipoproteins. Suppression by low density lipoprotein was clearly evident at molar ratios of low density lipoprotein to stimulatory lipoproteins of 1:3 or less. Reconstitution of all lipoproteins to physiological concentrations was not stimulatory as a consequence of the suppressive effects of low density lipoprotein. These data indicate that isolated plasma lipoproteins are capable of regulating the expression of two different procoagulant activities of peripheral blood mononuclear cells in vitro. The possibility that these interactions may be implicated in the association between certain types of hyperlipoproteinemias and thromboembolic disease merits study.