2017-10-10
2016-11-08
Coordinated by Kristina Nilsson Ekdahl (partner 1c) in collaboration with partners: 1a, 2, 4, 5, 6, 7 and 11.
The objectives of WP2 are to identify potential points of regulation of intravascular innate immunity in order to create new biomaterial surfaces and regulators in WP3, WP4 and WP7.
In particular, important points of intervention in the cross-talk between endothelial cells, PMNs and platelets and their relationship to the cascade systems will be investigated. The interactions between leukocytes and platelets are a major component of intravascular injury, where the platelets can serve as a bridge between leukocytes and the endothelium. The adhesive interactions between leukocytes and platelets are mediated by the Mac-1/GPIb interaction. Therefore, the efficacy of blocking these interactions for preventing vascular injury will be assessed. This will be done by in vitro whole blood assays – endothelial cell assays. Another task is the functional testing of Del-1 expressed by endothelial cells in lupus-like glomerulonephritis (TUD). Del-1 is an endogenous anti-inflammatory agent secreted by endothelial cells that inhibits LFA-1-dependent neutrophil recruitment and IL-17 dependent inflammation. The role of Del-1 will be assessed in a suitable mouse model.
Another issue addressed within this WP is to generate various types of nanoprofiled material surfaces for clarification of fundamental conditions for complement and contact system activation on material surfaces with respect to nanogeometry and for potential clinical applications involving contact with blood. A range of materials with defined nanoscale architecture and surface chemistry will be used for screening studies of complement activation and bacterial adhesion. Generation of nano-geometrical profile material surfaces applying molecular imprinted polymers (MIP) is also included in this WP. Macroporous polymer films will be produced to identify optimal nano-scale surface morphologies.