Kim, Bomin Yan, Ji-Jing Kang, Tae Kyeom Lee, Wook-Bin Jeong, Jong Cheol Yang, Jaeseok 2024-05-30T08:30:35Z 2024-05-30T08:30:35Z 2024-05-30 2024-05 0908-665X https://pubs.kist.re.kr/handle/201004/149951 Overexpression of human CD200 (hCD200) in porcine endothelial cells (PECs) has been reported to suppress xenogeneic immune responses of human macrophages against porcine endothelial cells. The current study aimed to address whether the above-mentioned beneficial effect of hCD200 is mediated by overcoming the molecular incompatibility between porcine CD200 (pCD200) and hCD200 receptor or simply by increasing the expression levels of CD200 without any molecular incompatibility across the two species. We overexpressed hCD200 or pCD200 using lentiviral vectors with V5 marker in porcine endothelial cells and compared their suppressive activity against U937-derived human macrophage-like cells (hMCs) and primary macrophages. In xenogeneic coculture of porcine endothelial cells and human macrophage-like cells or macrophages, hCD200-porcine endothelial cells suppressed phagocytosis and cytotoxicity of human macrophages to a greater extent than pCD200-porcine endothelial cells. Secretion of tumor necrosis factor-alpha, interleukin-1 beta, and monocyte chemoattractant protein-1 from human macrophages and expression of M1 phenotypes (inducible nitric oxide synthase, dectin-1, and CD86) were also suppressed by hCD200 to a greater extent than pCD200. Furthermore, in signal transduction downstream of CD200 receptor, hCD200 induced Dok2 phosphorylation and suppressed I kappa B phosphorylation to a greater extent than pCD200. The above data supported the possibility of a significant molecular incompatibility between pCD200 and human CD200 receptor, suggesting that the beneficial effects of hCD200 overexpression in porcine endothelial cells could be mediated by overcoming the molecular incompatibility across the species barrier rather than by simple overexpression effects of CD200. English Blackwell Publishing Inc. Molecular incompatibility between pig CD200 and human CD200 receptor in in vitro xenogeneic immune responses Article 10.1111/xen.12863 1 Xenotransplantation, v.31, no.3 Xenotransplantation 31 3 Y scie scopus 001223201600001 2-s2.0-85193276775 Medicine, Research & Experimental Transplantation Research & Experimental Medicine Transplantation Article OX2 GLYCOPROTEIN CELL SURVIVAL human CD200 human CD200 receptor molecular incompatibility porcine CD200 xenotransplantation