Contribution of the separate complement pathways for outcome and negative effects on innate immune functions during sepsis

• Antragsteller: Professor Dr. Niels Christoph Riedemann
• Fachliche Zuordnung: Orthopädie, Unfallchirurgie, rekonstruktive Chirurgie
• Förderung: Förderung von 2006 bis 2010
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 15252517

According to estimates in the USA and Germany, sepsis may account for more deaths per year than acute myocardial infarction. Yet, the underlying pathophysiological mechanisms leading to the clinically defined symptoms of sepsis are poorly understood. Recent publications have revealed an important role of the complement split product C5a being responsible for harmful effects during sepsis. Complement activation can occur through different mechanisms activating three known separate pathways. The end point of complement activation always involves formation of the potent inflammatory C5a and the terminal membrane attack complex (MAC). C5a will trigger significant changes in intracellular signaling of immune competent cells leading to acute inflammatory responses (Ü2 radical production etc.). However, activation of C5a in an uncontrolled manner during sepsis will lead to a shut down of such immune functions. Until now the triggers and the contribution of the separate complement pathways leading to formation of C5a during sepsis are not known in detail. The goal of this project is to define the contribution of the 3 separate complement pathways for harmful effects of complement activation during sepsis. The possibility to specifically block the main contributing complement pathway with antibodies or antagonists represents a potential preventive strategy for patients at high risk of developing sepsis and will be investigated later in humans based on the results of the outlined proposed studies.

• DFG-Verfahren: Sachbeihilfen