Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor.
Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor.
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DOI：
10.1111/xen.12236
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发表时间：
2016-05
影响因子：
3.9
通讯作者：
Karavi K
中科院分区：
文献类型：
--
作者：
Burdorf L;Riner A;Rybak E;Salles II;De Meyer SF;Shah A;Quinn KJ;Harris D;Zhang T;Parsell D;Ali F;Schwartz E;Kang E;Cheng X;Sievert E;Zhao Y;Braileanu G;Phelps CJ;Ayares DL;Deckmyn H;Pierson RN 3rd;Azimzadeh AM;Dandro A;Karavi K
在这里，我们询问血小板GPIb和GPIIb/IIIa受体是否调节GalTKO.hCD46猪肺异种移植物灌注期间的血小板隔离和活化。用肝素化的新鲜人血灌注GalTKO.hCD46转基因猪肺。将αGPIb Fab（6 B4，10 mg/L血液，n=6）、αGPIIb/IIIa Fab（ReoPro，3.5 mg/L血液，n=6）或两种药物（n=4）给予灌注液的灌注结果与另外2组进行比较，其中供体猪接受DDAVP，3μg/kg（预先耗尽pVWF，主要GPIb配体），有或无αGPIb（每组n=6）。αGPIb、αGPIb+DDAVP和αGPIb+αGPIIb/IIIa组血小板聚集明显延迟。当猪用DDAVP预处理，有或没有αGPIb Fab处理时，中位肺“存活”显著更长（>240 vs. 162 min参考，p=0.016），并且血小板活化（如CD 62 P和βTG）显著抑制。肺血管阻力升高在任何组中均未显著减弱，并且与残留血栓素和组胺的产生有关。GPIb-VWF和GPIIb/IIIa轴在GalTKO.hCD46肺异种移植物损伤期间的血小板隔离和凝血级联激活中起重要作用。在该异种肺排斥模型中，GPIb阻断剂显著降低血小板活化并延迟血小板隔离，通过添加αGPIIb/IIIa阻断剂或从猪肺中去除VWF来放大该效应。
Here we ask whether platelet GPIb and GPIIb/IIIa receptors modulate platelet sequestration and activation during GalTKO.hCD46 pig lung xenograft perfusion. GalTKO.hCD46 transgenic pig lungs were perfused with heparinized fresh human blood. Results from perfusions in which αGPIb Fab (6B4, 10mg/L blood, n=6), αGPIIb/IIIa Fab (ReoPro, 3.5mg/L blood, n=6), or both drugs (n=4) were administered to the perfusate were compared to 2 additional groups in which the donor pig received DDAVP, 3μg/kg (to pre-deplete pVWF, the main GPIb ligand), with or without αGPIb (n=6 each). Platelet sequestration was significantly delayed in αGPIb, αGPIb+DDAVP and αGPIb+αGPIIb/IIIa groups. Median lung “survival” was significantly longer (>240 vs. 162min reference, p=0.016), and platelet activation (as CD62P and βTG) were significantly inhibited, when pigs were pre-treated with DDAVP, with or without αGPIb Fab treatment. Pulmonary vascular resistance rise was not significantly attenuated in any group, and was associated with residual thromboxane and histamine elaboration. The GPIb-VWF and GPIIb/IIIa axes play important roles in platelet sequestration and coagulation cascade activation during GalTKO.hCD46 lung xenograft injury. GPIb blockade significantly reduces platelet activation and delays platelet sequestration in this xenolung rejection model, an effect amplified by adding αGPIIb/IIIa blockade or depletion of VWF from pig lung.
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影响因子：
6.2
作者：
Candinas, D;Lesnikoski, BA;Bach, FH
通讯作者：
Bach, FH
影响因子：
4.8
作者：
GOTO, S;SALOMON, DR;RUGGERI, ZM
通讯作者：
RUGGERI, ZM
影响因子：
3.4
作者：
Kang, HJ;Lee, G;Kim, YT
通讯作者：
Kim, YT
影响因子：
20.1
作者：
Bledzka K;Smyth SS;Plow EF
通讯作者：
Plow EF
影响因子：
4.4
作者：
Ekser B;Burlak C;Waldman JP;Lutz AJ;Paris LL;Veroux M;Robson SC;Rees MA;Ayares D;Gridelli B;Tector AJ;Cooper DK
通讯作者：
Cooper DK