Preview

PDF, German - main document Download (473kB) | Terms of use

Abstract

Peritoneal adhesions affect up to 93 % of patients after abdominal surgery and can lead to ileus, chronic pain and infertility. Building on our previous work, this project investigated the pathophysiological role of neutrophil extracellular traps (NETs) in adhesion formation and evaluated DNases (dornase alfa, NTR 10) as a therapeutic option. In a standardized murine laparotomy model, NET-deficient PAD4-knockout mice showed a significant reduction in adhesions, whereas Dnase1^−/− and Dnase1l3^−/− mice exhibited markedly increased adhesion scores. DNase application reduced the adhesion burden by up to 80 % in three surgical settings—laparotomy, anastomosis and serosal abrasion—without impairing wound healing. Transcriptomic analyses revealed DNase-mediated down-regulation of inflammatory signalling pathways, particularly those involved in leukocyte activation. Human adhesion tissue contained dense NET networks and DNase1L3 signals, confirming clinical relevance. The core findings published in iScience (Elrod et al., 2023) demonstrate that NETs form the initial—and essential—scaffold for adhesions, and that DNases effectively prevent their development. Within this project we also examined the same process in peritoneal dialysis. Complementary reviews highlight the potential of NET-targeted therapies to become a new standard for adhesion prophylaxis. We are currently investigating additional inhibitors of NETs and examining the crosstalk between neutrophils and macrophages in adhesion formation.