Porcine endothelium induces DNA–histone complex formation in human whole blood: a harmful effect of histone on coagulation and endothelial activation

• DOI: 10.1111/xen.12264
• Publication Date: 2016-09-10T05:13:48Z
• Authors: Hyun Ju Yoo; Ji‐Eun Kim; Ja Yoon Gu; Sae Bom Lee; Hyun Joo Lee; Ho Young Hwang; Yoohwa Hwang; Young Tae Kim; Hyun Kyung Kim
• Keywords: Xenotransplantation

Neutrophils play a role in xenograft rejection. When neutrophils are stimulated, they eject the DNA-histone complex into extracellular space, called neutrophil traps (NET). We investigated whether NET formation actively occurs and contributes to coagulation endothelial activation.Human whole blood was incubated with porcine aortic cells (pEC) from wild-type or α1,3-galactosyltransferase gene-knockout (GTKO) pigs. In supernatant plasma human blood, level of measured by ELISA, thrombin generation using calibrated automated thrombogram. Histone-induced tissue factor adhesion molecule expression were flow cytometry.pEC both GTKO pigs significantly induced blood. The produced shortened time clotting time. Histone alone dose-dependently pEC. Aurintricarboxylic acid pretreatment partially inhibited pEC-induced formation.DNA-histone generated upon xenotransplantation is novel target inhibit activation. To prevent expression, strategy block soluble histone may be required xenotransplantation.