Membrane Enhanced Complement Control Reduces Endothelial Cell Activation and Injury

Ischemia reperfusion injury and cardiopulmonary bypass in heart transplantation lead to an intense inflammatory response with complement activation and deposition modulating endothelial cell activation. The objective of this study was to determine whether a membrane‐targeted anti‐complement therapy would offer improved protection from complement‐mediated injury. We hypothesized that enhancing complement control of endothelial cell membranes with vaccinia virus complement control protein (VCP) will reduce complement deposition and endothelial cell activation when cells are incubated with complement pre‐activated plasma. Human umbilical vein endothelial cells (HUVECs) were treated to display VCP using a novel liposome‐based delivery system. Human blood was placed in plastic tubes and complement activated by rocking for 2.5 h at 37°C. Cells were incubated with plasma from plastic‐contact activated blood, and assessed for deposition of C3 and MAC, and expression of ICAM and VCAM. Cells enhanced with VCP had reduced C3, MAC, ICAM and VCAM as compared to untreated controls (p<0.05). We conclude that a membrane bound anti‐complement agent is highly effective in protecting endothelial cells challenged with complement activated plasma. Future in vivo studies will need to be performed to establish the potential clinical use of our liposomal‐based therapy in heart transplantation.