Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection
Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection
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DOI：
10.1111/j.1399-3089.2011.00633.x
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发表时间：
2011-03-01
影响因子：
3.9
通讯作者：
Pierson, Richard N., III
中科院分区：
文献类型：
--
作者：
Nguyen, Bao-Ngoc H.;Azimzadeh, Agnes M.;Pierson, Richard N., III
背景：半乳糖基转移酶基因敲除(GalTKO)猪为评价Gal抗原在异种肺超急性排斥反应中的作用提供了独特的工具。结果：GALTKO肺存活时间为132+/-52min，野生型为10+/-9min(P=0.001)，hDAF+/+肺为45+/-60min(P=0.18)。与野生型或hDAF+/+肺不同，GalTKO肺表现出稳定的生理血流和肺血管阻力(PVR)，直到移植物死亡前不久，类似于自体肺灌流。与野生型或hDAF+/+肺相比，GalTKO肺早期(15分钟和60分钟)补体(C3a)、血小板活化和肺内血小板沉积显著减少。然而，GalTKO肺吸收细胞毒性抗非Gal抗体并产生高水平的凝血酶；它们的死亡与PVR增加、毛细血管充血、血管内血栓和CD41强沉积有关。结论：总之，GalTKO肺受到实质保护，但除了抗Nal抗体和补体外，血小板黏附和非生理性血管内凝血参与了Gal非依赖性肺损伤机制。
Background:Galactosyl transferase gene knock-out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection.Methods:We perfused GalTKO miniature swine lungs with human blood. Results were compared with those from previous studies using wild-type and human decay-accelerating factor-transgenic (hDAF+/+) pig lungs.Results:GalTKO lungs survived 132 +/- 52 min compared to 10 +/- 9 min for wild-type lungs (P = 0.001) and 45 +/- 60 min for hDAF+/+ lungs (P = 0.18). GalTKO lungs displayed stable physiologic flow and pulmonary vascular resistance (PVR) until shortly before graft demise, similar to autologous perfusion, and unlike wild-type or hDAF+/+ lungs. Early (15 and 60 min) complement (C3a) and platelet activation and intrapulmonary platelet deposition were significantly diminished in GalTKO lungs relative to wild-type or hDAF+/+ lungs. However, GalTKO lungs adsorbed cytotoxic anti-non-Gal antibody and elaborated high levels of thrombin; their demise was associated with increased PVR, capillary congestion, intravascular thrombi and strong CD41 deposition not seen at earlier time points.Conclusions:In summary, GalTKO lungs are substantially protected from injury but, in addition to anti-non-Gal antibody and complement, platelet adhesion and non-physiologic intravascular coagulation contribute to Gal-independent lung injury mechanisms.