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.
Highlights
Neutrophils are known to produce neutrophil extracellular traps (NETs) of decondensed DNA and histones that trap and immobilize microbial pathogens, e.g., bacteria/fungi [2] or small inert nanoparticles [3]
We have selected for further detailed analysis the sample of tissue of Patient 1 being the part on the pancreas in the interface between normal tissue and necrosis area (Figure 2) and of Patient II being the part of peritoneum at the interface of healthy and necrotic areas (Figure 3)
Hematoxylin and eosin staining of the pancreas of Patient I demonstrated that a part of the organ still displayed a regular morphology, while other areas were completely destroyed by necrosis
Summary
Neutrophils are known to produce neutrophil extracellular traps (NETs) of decondensed DNA and histones that trap and immobilize microbial pathogens, e.g., bacteria/fungi [2] or small inert nanoparticles [3]. Whereas neutrophil extravasation plays an important role in mediating immune response [5] and was reportedly related to inflammatory insults of the invaded tissues [6], it has recently been reported that neutrophils patrol several body tissues that are not inflamed [7], protecting internal organs, exocrine glands, and their ducts from invading intestinal bacteria [8]. Massive tissue necrosis occurs in the abdominal cavity. Pancreatic necrosis present early as acute necrotic collections and are organized and separated from adjacent healthy tissues by granulation tissue (“walled-off necrosis”) [11]. These may form a provisionary tissue barrier separating necrotic areas from remains of viable tissue To check this possible involvement, we analyzed a series of necropsy samples of patients of Lviv Regional Clinical Hospital, who have died from multi-organ failure and systemic toxicity of massive inflammation in the abdominal region
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