Neutrophil granulocytes play an important role in the human immune system, as they constitute the first line of defense against invading pathogens such as bacteria, fungi, and viruses. To guarantee the best performance, neutrophils have a large set of options in fighting pathogens, most of which have been known for a long time. However, a new mechanism of host defense was discovered in 2004, the formation of Neutrophil Extracellular Traps (NETs). NETs consist of chromatin fibers and antimicrobial proteins. Since chromatin fibers are sticky structures, NETs can trap the pathogens, and then kill them due to their granular proteins, preventing the spreading of infections and facilitating the digestion of the pathogens by macrophages.

Yet there are two sides to each coin, and although NETs are very effective in the host defense, they also present certain autoantigens to the immune system. Autoantibodies directed against NET constituents can cause autoimmune diseases such as lupus erythematodes and several types of vasculitis. Several recent studies indicated that NETs influence the functions of cells of the human innate and adaptive immune system such as T-cells and dendritic cells. Surprisingly there is no data available so far how NETs influence the functions of neutrophils. Since neutrophils represent the most abundant inflammatory cell population at sites of acute infection/inflammation, NETs-mediated effects on neutrophils can have a major impact on the inflammatory process.

This thesis shall investigate the influence of NETs on primary human neutrophils in vitro. We will focus on cell survival, activation and certain effector mechanisms, such as ROS-production, NET release, phagocytosis and cytokine production. Results of the study are expected to provide novel knowledge regarding the regulatory properties of NETs and may lead to the identification of novel targets for the therapy of inflammatory and/or autoimmune diseases.