Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates.
Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates.
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DOI：
10.1111/jth.12295
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
McCarty OJ
中科院分区：
文献类型：
--
作者：
Puy C;Tucker EI;Wong ZC;Gailani D;Smith SA;Choi SH;Morrissey JH;Gruber A;McCarty OJ
Inorganic polyphosphates (polyP), which are secreted by activated platelets (short chain polyP) and accumulate in some bacteria (long chain polyP), support the contact activation of factor XII (FXII), and accelerate the activation of factor XI (FXI). The aim of the present study was to evaluate the role of FXI in polyP-mediated coagulation activation and experimental thrombus formation Pretreatment of plasma with antibodies that selectively inhibit FXI activation by activated FXII (FXIIa) or factor IX (FIX) activation by activated FXI (FXIa) were not able to inhibit the procoagulant effect of long or short polyP in plasma. In contrast, the FXIIa inhibitor, corn trypsin inhibitor (CTI), blocked the procoagulant effect of long and short polyP in plasma. In a purified system, long polyP significantly enhanced the rate of FXII and prekallikrein (PK) activation, and the activation of FXI by thrombin, but not by FXIIa. In FXI-deficient plasma, long polyP promoted clotting of plasma in a FIX-dependent manner. In a purified system, the activation of FXII and PK by long polyP promoted FIX activation and prothombin activation. In an ex vivo model of occlusive thrombus formation, inhibition of FXIIa with CTI but not of FXI with a neutralizing antibodies abolished the prothrombotic effect of long polyP. We propose that long polyP promotes FXII-mediated blood coagulation bypassing FXI. Accordingly, some polyP containing pathogens may have evolved strategies to exploit polyP-initiated FXII activation for virulence, and selective inhibition of FXII may improve the host response to pathogens.
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DOI：
10.1084/jem.20052458
发表时间：
2006-03-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kleinschnitz C;Stoll G;Bendszus M;Schuh K;Pauer HU;Burfeind P;Renné C;Gailani D;Nieswandt B;Renné T
通讯作者：
Renné T
影响因子：
4.2
作者：
Kuhli, C;Scharrer, I;Hattenbach, LO
通讯作者：
Hattenbach, LO
影响因子：
4.8
作者：
Grundt, H;Nilsen, DWT;Fagertun, HE
通讯作者：
Fagertun, HE
影响因子：
82.9
作者：
Herwald, H;Mörgelin, M;Björck, L
通讯作者：
Björck, L
影响因子：
4.8
作者：
KUMBLE, KD;KORNBERG, A
通讯作者：
KORNBERG, A