Schwartz B S, Levy G A, Curtiss L K, Fair D S, Edgington T S
J Clin Invest. 1981 Jun;67(6):1650-8. doi: 10.1172/jci110201.
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.
在分析脂蛋白对淋巴细胞功能的影响过程中，观察到分离出的人血浆脂蛋白的生理浓度具有不同能力，可在体外迅速增强人外周血单核细胞促凝活性的表达。在严格的剂量依赖性方式下，极低密度脂蛋白、中间密度脂蛋白和高密度脂蛋白在6小时孵育期间增强了活细胞的表面表达以及促凝活性的总细胞含量。极低密度脂蛋白诱导凝血活酶活性表达最大增加6.7倍，该活性与组织因子一致，因为它依赖于因子VII、X和II。中间密度脂蛋白和高密度脂蛋白均诱导一种不同的促凝活性增加约12倍，这种促凝活性似乎是一种直接的凝血酶原激活剂。这种凝血酶原酶依赖于钙，被2.5 mM二异丙基氟磷酸抑制，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活性，而是积极抑制刺激脂蛋白诱导的两种促凝活性的产生。在低密度脂蛋白与刺激脂蛋白的摩尔比为1:3或更低时，低密度脂蛋白的抑制作用明显。由于低密度脂蛋白的抑制作用，将所有脂蛋白重构至生理浓度并无刺激作用。这些数据表明，分离出的血浆脂蛋白能够在体外调节外周血单核细胞两种不同促凝活性的表达。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关联有关，这一可能性值得研究。
