Up-regulation of fibrinogen-like protein 2 in porcine endothelial cells by xenogeneic CD40 signal |
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Authors: | Bumrae Cho Eun Mi Lee Sunghoon Hurh Byeong Chun Lee |
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Affiliation: | 1. Biotechnology Research Institute, Mgenplus Co., Ltd., Seoul, Republic of Korea;2. Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea;3. Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea;4. Center for Medical Innovation, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea;5. Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea;6. Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea |
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Abstract: | 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. |
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Keywords: | Fibrinogen-like protein 2 CD40-CD40L interaction endothelial cells xenotransplantation thrombosis |
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