Xenogeneic interaction between human CD40L and porcine CD40 activates porcine endothelial cells through NF-kappaB signaling.
Xenotransplantation is a promising alternative to overcome donor shortage in transplantation. CD40 molecule plays an important role in the interaction of T cells with antigen-presenting cells and in the activation of vascular endothelial cells. We investigated whether the xenogeneic interaction between human CD40L (hCD40L) on T cells and porcine endothelial CD40 (pCD40) can activate porcine endothelial cells (PECs). The interaction between hCD40L and pCD40 induced the expression of chemokines on PECs as well as MHC and adhesion molecules. Furthermore, NF-kappaB signaling was activated in HEK 293 cells expressing pCD40 and PECs by stimulation with hCD40L+ Jurkat T clones. Both anti-CD40L neutralizing antibodies and NF-kappaB signal inhibitors interfered with immune activation of PECs. Overall, this study shows that xenogeneic interaction between hCD40L and pCD40 can activate PECs through NF-kappaB signaling, and therefore may contribute to acute vascular rejection in xenotransplantation.
Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Inho
I
Choi
Sung Dae
SD
Kim
Bumrae
B
Cho
Donghee
D
Kim
Dongkyoo
D
Park
Hyun Sook
HS
Koh
Bo-Yoon
BY
Kim
Jae Young
JY
Kim
Jaeseok
J
Yang
Curie
C
Ahn
D000595:Amino Acid Sequence; D000818:Animals; D019013:CD40 Antigens / Q000737:chemistry / Q000378:metabolism*; D023201:CD40 Ligand / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature / Q000378:metabolism*
D019013:CD40 Antigens; D016328:NF-kappa B; D023201:CD40 Ligand