Prevention of abdominal adhesion formation using Dnases: pathogenesis and translation

• Applicant: Professor Dr. Michael Boettcher
• Subject Area: Pediatric and Adolescent Medicine ; General and Visceral Surgery
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446358093

Adhesions are bridges between peritoneum and the viscera, which result from maladaptive healing of surgical tissue damage. Adhesions frequently complicate abdominal interventions and lead to small intestinal obstruction, female infertility, chronic pain, and increased complications during reoperative procedures. This results in millions of patients being affected with subsequent treatments estimating to cost approximately two billion euros per year in the USA.Current preventive measures are either ineffective or complicated to handle and are thus rarely utilized outside experimental studies. The development of novel therapeutics is limited since the molecular mechanism of peritoneal healing is poorly characterized.Neutrophils, the predominat leukocytes of acute inflammatory reactions, are rapidly recruited to sites of tissue damage. In preliminary experiments we demonstrated that neutrophils generate extracellular traps (NETs) at sites of abdominal surgical injury. NETs are lattices of intact chromatin filaments that are decorated with biologically active proteins and peptides. NETs contribute to homeostatic and pathological inflammation, including autoimmune disease, sepsis, and ischemia-reperfusion injury. Using an experimental model in mice, we were able to prove that therapeutic targeting of NETs by DNA- degrading enzymes (DNase) prevented abdominal adhesions. Thus, we propose to further investigate the role of NETs in the pathogenesis of adhesions using murine models and human specimen.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Tobias Fuchs