New strategies to prevent vascular leak in acute inflammation

Sepsis is a dreaded complication of bacterial infections that, despite advanced intensive care, can lead to circulatory collapse and organ failure with high mortality rates. Increasing prevalence of antibiotic resistance contributes to difficulties in successfully treating these conditions. An essential component in the development of the disease is damage to the blood vessels of the lungs, resulting in leakage of blood plasma into the lung tissue. The lung injury is mainly due to the activation of white blood cells, particularly neutrophilic granulocytes. We have shown that proteins released from storage vesicles in the granulocytes (e.g. HBP/azurocidin) strongly contribute to the impairment of the blood vessel barrier function during inflammation. The research program aims to further elucidate mechanisms for the impact of white blood cells on blood vessel integrity in inflammatory disease states including sepsis. In particular, it will investigate new possibilities to therapeutically counteract the harmful activity of granule proteins in acute systemic inflammation. The program will hopefully establish a completely new approach to the treatment of complications in severe infectious conditions which may lead to the development of unique drugs in this field.