title: Neutrophil Extracellular Traps Form a Barrier between Necrotic and Viable Areas in Acute Abdominal Inflammation.
abstract: Neutrophils form neutrophil extracellular traps (NETs) of decondensed DNA and histones that trap and immobilize particulate matter and microbial pathogens like bacteria. NET aggregates reportedly surround and isolate large objects like monosodium urate crystals, which cannot be sufficiently cleared from tissues. In the setting of acute necrotizing pancreatitis, massive tissue necrosis occurs, which is organized as pancreatic pseudocysts (1). In contrast to regular cysts, these pseudocysts are not surrounded by epithelial layers. We hypothesize that, instead, the necrotic areas observed in necrotizing pancreatitis are isolated from the surrounding healthy tissues by aggregated NETs. These may form an alternative, putatively transient barrier, separating necrotic areas from viable tissue. To test this hypothesis, we investigated histological samples from the necropsy material of internal organs of two patients with necrotizing pancreatitis and peritonitis accompanied by multiple organ failure. Tissues including the inflammatory zone were stained with hematoxylin and eosin and evaluated for signs of inflammation. Infiltrating neutrophils and NETs were detected by immunohistochemistry for DNA, neutrophil elastase (NE), and citrullinated histone H3. Interestingly, in severely affected areas of pancreatic necrosis or peritonitis, chromatin stained positive for NE and citrullinated histone H3, and may, therefore, be considered NET-derived. These NET structures formed a layer, which separated the necrotic core from the areas of viable tissue remains. A condensed layer of aggregated NETs, thus, spatially shields and isolates the site of necrosis, thereby limiting the spread of necrosis-associated proinflammatory mediators. We propose that necrotic debris may initiate and/or facilitate the formation of the NET-based surrogate barrier.
authors: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany; Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
authors: Rostyslav
authors: R
authors: Bilyy
authors: Lviv Regional Clinical Hospital , Lviv , Ukraine.
authors: Volodymyr
authors: V
authors: Fedorov
authors: Danylo Halytsky Lviv National Medical University , Lviv , Ukraine.
authors: Volodymyr
authors: V
authors: Vovk
authors: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Internal Medicine 1 - Gastoenterology, Universitätsklinikum Erlangen , Erlangen , Germany.
authors: Moritz
authors: M
authors: Leppkes
authors: Danylo Halytsky Lviv National Medical University , Lviv , Ukraine.
authors: Tetiana
authors: T
authors: Dumych
authors: Danylo Halytsky Lviv National Medical University , Lviv , Ukraine.
authors: Valentyna
authors: V
authors: Chopyak
authors: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen , Erlangen , Germany.
authors: Georg
authors: G
authors: Schett
authors: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen , Erlangen , Germany.
authors: Martin
authors: M
authors: Herrmann
keywords: inflammation; neutrophil elastase; neutrophil extracellular traps; neutrophils; sepsis