The anticoagulant effect of the human secretory phospholipase A2 on blood plasma and on a cell-free system is due to a phospholipid-independent mechanism of action involving the inhibition of factor Va.
The anticoagulant effect of the human secretory phospholipase A2 on blood plasma and on a cell-free system is due to a phospholipid-independent mechanism of action involving the inhibition of factor Va.
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人分泌型磷脂酶 A2 对血浆和无细胞系统的抗凝作用是由于涉及抑制因子 Va 的磷脂独立作用机制所致。
DOI：
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Cassian Bon
中科院分区：
文献类型：
--
作者：
C. Mounier;Peet A. Franken;Hubertus M. Verheij;Cassian Bon
血小板通过导致血栓形成和通过增加血液凝固的效率在止血中发挥核心作用。我们以前已经表明，血小板含有II组分泌型磷脂酶A2（sPLA2 grII），激活后释放到细胞外介质中，但不能刺激血小板。我们目前报道了一项调查的假定参与人sPLA2 grII（hsPLA2 grII）在凝血过程中，无论是在存在和不存在活化血小板。我们表明，这种酶的血小板活化的血浆，即使在存在的时间缩短。血小板对凝血的积极作用至少部分地与构成hsPLA2 grII的潜在靶点的促凝血磷脂在细胞表面的出现相关。因此，我们研究了这种酶的抗凝作用的酶活性的参与。我们观察到，SrCl2启动凝血级联反应的CaCl2的替代没有抑制，而是增加了hsPLA2 grII的抑制作用。此外，hsPLA2 grII水解只有一小部分的血小板磷脂，它不影响血浆磷脂。两者合计，这些观察结果强烈表明，hsPLA2 grII对血液凝固的主要作用不涉及磷脂的水解，与II组蛇毒磷脂酶A2从响尾蛇terrificus的强抗凝血作用相反。我们接下来研究了hsPLA2 grII影响凝血级联反应的哪一步。使用纯化的凝血因子，我们证明hsPLA2 grII强烈抑制凝血酶原酶活性。这种抑制作用是独立的磷脂的存在下，但需要因子Va，导致hsPLA2 grII抑制该因子的假设。此外，hsPLA2 grII的抗凝作用，观察到正常和因子X缺乏的血浆，但不对因子V缺乏的血浆。总之，hsPLA2 grII的抗凝作用是基于涉及抑制因子Va的非酶促作用机制。
Blood platelets play a central role in haemostasis by leading to plug formation and by increasing the efficiency of blood coagulation. We have previously shown that blood platelets contain a group II secretory phospholipase A2 (sPLA2 grII) which is released into the extracellular medium upon activation but is unable to stimulate blood platelets. We presently reported an investigation of the putative involvement of the human sPLA2 grII (hsPLA2 grII) in the coagulation process, both in the absence and in the presence of activated platelets. We show that this enzyme prolongs the recalcification time of blood plasma even in the presence of activated platelets. The positive action of blood platelets on coagulation is correlated, at least in part, with the appearance at the cellular surface of procoagulant phospholipids which constitute a potential target for hsPLA2 grII. We therefore investigated the involvement of its enzymatic activity in the anticoagulant effect of this enzyme. We observed that the replacement of CaCl2 by SrCl2 to initiate the coagulation cascade did not suppress, but rather increased, the inhibitory action of hsPLA2 grII. Moreover, hsPLA2 grII hydrolyzed only a minor proportion of platelet phospholipids, and it did not affect plasma phospholipids. Taken together, these observations strongly suggest that the major action of hsPLA2 grII on blood coagulation does not involve the hydrolysis of phospholipids, in contrast with the strong anticoagulant effect of the group II venom phospholipase A2 from Crotalus durrissus terrificus. We next studied which step of the coagulation cascade was affected by hsPLA2 grII. Using purified coagulation factors, we demonstrated that hsPLA2 grII strongly inhibited the prothrombinase activity. This inhibitory effect was independent of the presence of phospholipids but required factor Va, leading to the hypothesis that hsPLA2 grII inhibited this factor. Further, the anticoagulant effect of hsPLA2 grII was observed on normal and factor-X-deficient plasma, but not on factor-V-deficient plasma. In conclusion, the anticoagulant action of hsPLA2 grII is based on a nonenzymatic mechanism of action involving the inhibition of factor Va.
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影响因子：
2.9
作者：
DAVIE, EW;FUJIKAWA, K;KISIEL, W
通讯作者：
KISIEL, W
II 组磷脂酶 A2 表达的反义抑制可阻断 P388D1 细胞产生前列腺素 E2。
DOI：
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发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Barbour,SE;Dennis,EA
通讯作者：
Dennis,EA
影响因子：
7
作者：
P. Elsbach;Jerrold Weiss
通讯作者：
P. Elsbach;Jerrold Weiss
胶原诱导血小板和血小板衍生微粒中阴离子磷脂的暴露。
DOI：
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发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Thiagarajan,P;Tait,JF
通讯作者：
Tait,JF
纯化的 14-kDa 磷脂酶 A2 对无细胞凝血酶原酶复合物的抑制作用的决定因素。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Inada,M;Crowl,RM;Bekkers,AC;Verheij,H;Weiss,J
通讯作者：
Weiss,J