Oguchi A, Morioka M, Obi N, Nishida J, Kinoshita T
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. oguchan#@avis.ne.jp
Int J Hematol. 1999 Feb;69(2):119-25.
It is known that tissue factor (TF) activity depends on cell membrane phospholipids. However, the mechanism involved in the regulation of TF activity by the modulation of the phospholipids has not yet been described in detail. To determine whether some mediators regulate TF activity by such a mechanism, we investigated the effect of platelet activating factor (PAF). Addition of PAF to TF-expressed monocytes caused a rapid and marked increase in the activity, but no increase in the antigen. Kinetic analyses were performed on TF-expressed monocytes with or without the addition of PAF, and on purified TF. The former revealed that the activity enhancement by PAF was associated with reduced Km, with Vmax remaining unaltered. The latter showed that the additional phosphatidylserine produced greater TF activity in purified TF, with an alteration pattern of kinetic parameters similar to that observed in the addition of PAF. From these results, we conclude that PAF regulates TF activity at the cell surface by alteration of the phospholipid composition of the membrane, and not by fresh production of TF apoprotein. The role of PAF as described in this paper must be one of the major regulatory systems in TF activity.
已知组织因子(TF)的活性依赖于细胞膜磷脂。然而,通过调节磷脂来调控TF活性所涉及的机制尚未得到详细描述。为了确定某些介质是否通过这种机制调节TF活性,我们研究了血小板活化因子(PAF)的作用。向表达TF的单核细胞中添加PAF会导致活性迅速且显著增加,但抗原无增加。对添加或未添加PAF的表达TF的单核细胞以及纯化的TF进行了动力学分析。前者显示PAF增强活性与Km降低有关,Vmax保持不变。后者表明额外的磷脂酰丝氨酸在纯化的TF中产生了更高的TF活性,其动力学参数的改变模式与添加PAF时观察到的相似。从这些结果中,我们得出结论,PAF通过改变膜的磷脂组成而非通过新产生TF载脂蛋白来在细胞表面调节TF活性。本文所述PAF的作用必定是TF活性的主要调节系统之一。