Miyazaki K
Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 2000 Sep;75(5):347-56.
Hyper-acute rejection after cardiac xenotransplantation has been extensively studied, but its morphological changes have not been adequately elucidated yet. We investigated the morphological changes in two kinds of cardiac xenotransplantation models, guinea pig hearts in rats and hamster hearts in sensitized rats, in terms of histology, immunohistochemistry. TdT-mediated dUTP nick-end labeling (TUNEL) and ultrastructure. Four guinea pig hearts were heterotopically transplanted to rats and four hamster hearts to sensitized rats by the modified technique of Ono and Lindsey. In the hamster-to-rat model, the rats were treated with a hamster skin tissue at two weeks before transplantation. Rejection of the grafts was diagnosed from cessation of the graft heart contraction. Immunohistochemically, C3 was deposited along all vessels including coronary vessels, arterioles, venules and capillaries, and IgM was deposited along major vessels in the guinea pig grafts; it was vice versa in the hamster grafts. In the guinea pig grafts, TUNEL showed positive staining in endothelial cells and myocytes, whereas no positive signal was shown in the rejected hamster hearts. Transmission electron microscopy revealed platelet aggregations in the vessels of guinea pig-to-rat and hamster-to-sensitized rat cardiac xenografts. In the guinea pig-to-rat cardiac xenografts, capillary walls were thin with a high electron density and the number of pinocytotic vesicles was reduced. Also several nuclei of the endothelial cells showed pyknosis and some nuclei were fragmented. On the other hand, these findings were not typical in the hamster-to-sensitized rat cardiac xenografts. In conclusion, this study revealed thromboembolism of capillaries and impairment of the endothelial cells in the hyper-acutely rejecting cardiac xenografts. Apoptosis of myocytes and endothelial cells was shown to be involved only in the hyper-acutely rejecting guinea pig-to-rat cardiac xenografts. These results indicated variability in hyper-acute rejection.
心脏异种移植后的超急性排斥反应已得到广泛研究，但其形态学变化尚未得到充分阐明。我们从组织学、免疫组织化学、TdT介导的dUTP缺口末端标记（TUNEL）和超微结构方面，研究了两种心脏异种移植模型（大鼠体内的豚鼠心脏和致敏大鼠体内的仓鼠心脏）的形态学变化。采用改良的小野和林赛技术，将4个豚鼠心脏异位移植到大鼠体内，4个仓鼠心脏移植到致敏大鼠体内。在仓鼠-大鼠模型中，大鼠在移植前两周用仓鼠皮肤组织进行处理。根据移植心脏收缩停止来诊断移植物的排斥反应。免疫组织化学显示，C3沉积在包括冠状动脉、小动脉、小静脉和毛细血管在内的所有血管周围，IgM沉积在豚鼠移植物的主要血管周围；在仓鼠移植物中情况则相反。在豚鼠移植物中，TUNEL显示内皮细胞和心肌细胞呈阳性染色，而在发生排斥反应的仓鼠心脏中未显示阳性信号。透射电子显微镜显示，在豚鼠-大鼠和仓鼠-致敏大鼠心脏异种移植物的血管中有血小板聚集。在豚鼠-大鼠心脏异种移植物中，毛细血管壁薄，电子密度高，吞饮小泡数量减少。此外，一些内皮细胞核出现固缩，部分细胞核碎片化。另一方面，这些发现在仓鼠-致敏大鼠心脏异种移植物中并不典型。总之，本研究揭示了超急性排斥的心脏异种移植物中存在毛细血管血栓栓塞和内皮细胞损伤。仅在超急性排斥的豚鼠-大鼠心脏异种移植物中显示出心肌细胞和内皮细胞的凋亡。这些结果表明超急性排斥存在变异性。
