The effect of membrane composition on the hemostatic balance.
The effect of membrane composition on the hemostatic balance.
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膜成分对止血平衡的影响。
DOI：
10.1021/bi982538b
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Esmon,NL
中科院分区：
文献类型：
--
作者：
Smirnov,MD;Ford,DA;Esmon,CT;Esmon,NL
研究了激活蛋白C(APC)抗凝剂最佳激活凝血酶原和灭活凝血因子Va所需的磷脂组成。由磷脂酰乙醇胺(PE)和磷脂酰胆碱(PC)组成的囊泡对Va因子失活有较好的支持作用。然而，最佳的因子Va失活仍然需要相对较高浓度的磷脂酰丝氨酸(PS)。此外，在磷脂、PS和APC的固定浓度下，不含PE的囊泡永远不会达到含有PE的囊泡所能达到的Va因子失活速度。任何囊泡成分的多不饱和也是导致因子Va的APC失活的重要原因。因此，PE对因子Va的失活做出了PS不能模仿的重要贡献。在其他膜组分没有多不饱和的情况下，这种贡献取决于PE头基本身的存在和1，2脂肪酸的不饱和。尽管PE在最佳PS浓度下不影响凝血酶原激活率，但PE将PS∼的需求减少了10倍。凝血酶原Km(APP)和凝血因子Xa因子Va的Kd(APP)随PS浓度的增加而降低，在10−时达到最佳值，15%PS时无PE，而PE时仅为1%PS。脂肪酸多不饱和的影响微乎其微。狼疮抗凝剂免疫球蛋白在PE存在时对凝血酶原酶和凝血因子Va失活均有更强的抑制作用。与凝血酶原酶相比，APC的抑制程度明显更大，且更依赖于磷脂组成。因此，在正常和病理条件下，细胞磷脂组成的细微变化可能会不同地控制促凝和抗凝反应。
The phospholipid composition requirements for optimal prothrombin activation and factor Va inactivation by activated protein C (APC) anticoagulant were examined. Vesicles composed of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) supported factor Va inactivation relatively well. However, optimal factor Va inactivation still required relatively high concentrations of phosphatidylserine (PS). In addition, at a fixed concentration of phospholipid, PS, and APC, vesicles devoid of PE never attained a rate of factor Va inactivation achievable with vesicles containing PE. Polyunsaturation of any vesicle component also contributed significantly to APC inactivation of factor Va. Thus, PE makes an important contribution to factor Va inactivation that cannot be mimicked by PS. In the absence of polyunsaturation in the other membrane constituents, this contribution was dependent upon the presence of both the PE headgroup per se and unsaturation of the 1,2 fatty acids. Although PE did not affect prothrombin activation rates at optimal PS concentrations, PE reduced the requirement for PS ∼10-fold. TheKm(app)for prothrombin and theKd(app)for factor Xa-factor Va decreased as a function of increasing PS concentration, reaching optimal values at 10−15% PS in the absence of PE but only 1% PS in the presence of PE. Fatty acid polyunsaturation had minimal effects. A lupus anticoagulant immunoglobulin was more inhibitory to both prothrombinase and factor Va inactivation in the presence of PE. The degree of inhibition of APC was significantly greater and much more dependent on the phospholipid composition than that of prothrombinase. Thus, subtle changes in the phospholipid composition of cells may control procoagulant and anticoagulant reactions differentially under both normal and pathological conditions.