Cho Bumrae, Choi Inho, Lee Eun Mi, Hurh Sunghoon, Lee Byeong Chun, Ahn Curie
Biotechnology Research Institute, Mgenplus Co., Ltd., Seoul, Republic of Korea.
Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Anim Cells Syst (Seoul). 2018 Feb 1;22(2):92-99. doi: 10.1080/19768354.2018.1433718. eCollection 2018.
Acute humoral xenograft rejection (AHXR), characterized by thrombin generation and endothelial cell activation, should be overcome for the success of xenotransplantation. Fibrinogen-like protein 2 (fgl2) expressed on endothelial cells can convert prothrombin to thrombin directly, which indicates that the induced fgl2 expression in activated endothelial cells can contribute to thrombosis. In xenotransplant condition, the interaction between human CD40L and porcine endothelial CD40 can activate endothelial cells. In this study, we investigated the effect of endothelial cell activation through the interaction between human CD40L and porcine CD40 on fgl2 expression and its function as a direct prothrombinase. We found that CD40 stimulation up-regulated fgl2 expression as well as its enzymatic activity in porcine endothelial cells. Moreover, functional studies using knock-down system showed that the major factor converting human prothrombin to thrombin is fgl2 protein expressed on porcine endothelial cells. Overall, this study demonstrates that fgl2 expression can be induced by xenogeneic CD40 signal on endothelial cells and contribute to thrombin generation.
急性体液异种移植排斥反应（AHXR）的特征是凝血酶生成和内皮细胞活化，为实现异种移植的成功，必须克服这一反应。内皮细胞上表达的纤维蛋白原样蛋白2（fgl2）可直接将凝血酶原转化为凝血酶，这表明活化内皮细胞中诱导的fgl2表达可能导致血栓形成。在异种移植条件下，人CD40L与猪内皮细胞CD40之间的相互作用可激活内皮细胞。在本研究中，我们调查了通过人CD40L与猪CD40之间的相互作用激活内皮细胞对fgl2表达及其作为直接凝血酶原酶功能的影响。我们发现CD40刺激可上调猪内皮细胞中fgl2的表达及其酶活性。此外，使用敲低系统进行的功能研究表明，将人凝血酶原转化为凝血酶的主要因素是猪内皮细胞上表达的fgl2蛋白。总体而言，本研究表明，异种CD40信号可诱导内皮细胞表达fgl2，并促进凝血酶生成。
