WP5 Development and resolution
Development of amyloid deposits is a dynamic process at which both formation of new fibrils and degradation of assembled material occur in parallel. How these phenomena are initiated is not clear. In this workpackage we will study these processes on the cell and tissue levels. An established mouse model for systemic AA-amyloidosis (secondary amyloidosis occurring as a complication of certain chronic inflammatory diseases) is used but as part of the project we will develop an alternative cell culture system. This will help us to investigate whether fibrils in nature or synthetically made fibrils may be starting points for amyloidoses. Cell systems for the study of other forms of amyloidosis, including that derived from apolipoprotein A-I (a model for one form of familial amyloidosis) will also be created and used for studies of effects of enzymes on the resolution of amyloid deposits. The mouse model of AA-amyloidosis will be used to study the importance of the immune system for resolution of amyloid deposits. All amyloid deposits contain heparan sulfate and the importance of this substance will be determined in a cell culture system.