Neutrophil Extracellular Traps Induce Trypsin Activation, Inflammation, and Tissue Damage in Mice With Severe Acute Pancreatitis

Merza, Mohammed; Hartman, Hannes; Rahman, Milladur; Hwaiz, Rundk; Zhang, Enming; Renström, Erik; Luo, Lingtao; Mörgelin, Matthias; Regnér, Sara; Thorlacius, Henrik

doi:10.1053/j.gastro.2015.08.026

Cited by 209 publications

(226 citation statements)

References 42 publications

Supporting

Mentioning

206

Contrasting

Unclassified

Order By: Relevance

“…A number of innate and synthetic substances have demonstrated the ability to inhibit histone‐related toxicity based on surface charge alone, including plasma proteins (albumin,123 CRP14), polypeptides (polyglutamic acid126) and polysaccharides (heparin/heparanoids,111, 146 polysialic acid,147 bacterial O‐antigen148). Elevated histone‐degrading activated protein C (APC) levels are associated with better outcomes in sepsis115, 149 and trauma patients137; APC therapy is being evaluated for treatment of sepsis150 and pancreatitis 151.…”

Section: Therapeutic Strategies For Histone Detoxification In Pathologymentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Histones are positively charged nuclear proteins that facilitate packaging of DNA into nucleosomes common to all eukaryotic cells. Upon cell injury or cell signalling processes, histones are released passively through cell necrosis or actively from immune cells as part of extracellular traps. Extracellular histones function as microbicidal proteins and are pro‐thrombotic, limiting spread of infection or isolating areas of injury to allow for immune cell infiltration, clearance of infection and initiation of tissue regeneration and repair. Histone toxicity, however, is not specific to microbes and contributes to tissue and end‐organ injury, which in cases of systemic inflammation may lead to organ failure and death. This review details the processes of histones release in acute inflammation, the mechanisms of histone‐related tissue toxicity and current and future strategies for therapy targeting histones in acute inflammatory diseases.

show abstract

Section: Therapeutic Strategies For Histone Detoxification In Pathologymentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…A crucial role of neutrophils has been shown in patients with food allergy [73] and well documented in acute pancreatitis [15, 74, 75]. The neutrophil mediators cause trypsin activation, inflammation and may promote pathogenesis of pancreatitis [74] via IgE independent anaphylactic reactions [76].…”

Section: Role Of Inflammatory Cells In Food-allergen Mediated Pancreamentioning

confidence: 99%

Food-Induced Acute Pancreatitis

et al. 2017

View full text Add to dashboard Cite

Food allergy, a commonly increasing problem worldwide, defined as an adverse immune response to food. A variety of immune-related effector cells such as mast cells, eosinophils, neutrophils, and T cells are involved in food-related allergic responses categorized as IgE-mediated, non-IgE mediated, and mixed (IgE and non-IgE) depending upon underlying immunological mechanisms. The dietary antigens mainly target the gastrointestinal tract including pancreas that gets inflamed due to food allergy and leads acute pancreatitis. Reports indicate several food proteins induce pancreatitis; however, detailed underlying mechanism of food-induced pancreatitis is unexplored. The aim of the review is to understand and update the current scenario of food-induced pancreatitis. A comprehensive literature search of relevant research articles has been performed through PubMed and articles were chosen based on their relevance to food allergen mediated pancreatitis. Several cases in the literature indicating that acute pancreatitis has been provoked after the consumption of mustard, milk, egg, banana, fish, and kiwi fruits. Food-induced pancreatitis is an ignored and unexplored area of research. The review highlights the significance of food in the development of pancreatitis and draws the attention of physicians and scientists to consider food allergies as a possible cause for initiation of pancreatitis pathogenesis.

show abstract

“…Another outcome of neutrophil accumulation leading to build-up of polyelectrolytes into the extracellular space is proteolytic action of neutrophil proteases (elastase, cathepsin G protease, and proteinase-3) that are released as both free and as a part of the NET component and are very destructive within the surrounding tissue [13,14]. In effect, DNA and F-actin gathering at infectious sites originate from neutrophils and broken host cells.…”

Section: Dna and F-actin Accumulation In Extracellular Compartmentmentioning

confidence: 99%

Neutrophil extracellular traps as the main source of eDNA

Cieśluk¹,

Piktel²,

Wątek³

et al. 2017

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed DNA together with accompanying proteins, including histones and antimicrobial peptides released from activated neutrophils as part of the first-line defence against pathogens. Despite the protective role of neutrophils, a number of studies indicate that overproduction of NETs followed by accumulation of extracellular DNA (eDNA) and other negatively-charged polyelectrolytes (PE) such as F-actin, contribute to the pathogenesis of some diseases. Neutrophil extracellular traps are also recognised as the structural and functional support of microbial biofilms and should thus be considered as therapeutic targets. Importantly, the chemical nature of PE permits aggregate formation induced by a number of polycations occurring naturally in the human body, including cationic antimicrobial peptides. This review summarises recent reports focused on the clinical significance of NET-derived eDNA and PE and discusses the potential therapeutic strategies to limit the negative consequences of eDNA accumulation.

show abstract

Neutrophil Extracellular Traps Induce Trypsin Activation, Inflammation, and Tissue Damage in Mice With Severe Acute Pancreatitis

Cited by 209 publications

References 42 publications

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Food-Induced Acute Pancreatitis

Neutrophil extracellular traps as the main source of eDNA

Contact Info

Product

Resources

About