Neutrophil extracellular traps (NETs) are a combination of DNA fibers and granular proteins, such as neutrophil elastase (NE). NETs are released in the extracellular space in response to different stimuli. Carrageenan is a sulfated polysaccharide extracted from Chondrus crispus, a marine algae, used for decades in research for its potential to induce inflammation in different animal models. In this study, we show for the first time that carrageenan injection can induce NET release in a mouse model of acute peritonitis. Carrageenan induced NET release by viable neutrophils with NE and myeloperoxidase (MPO) expressed on DNA fibers. Furthermore, although this polysaccharide was able to stimulate reactive oxygen species (ROS) generation by peritoneal neutrophils, NADPH oxidase derived ROS were dispensable for NET formation by carrageenan. In conclusion, our results show that carrageenan-induced inflammation in the peritoneum of mice can induce NET formation in an ROS-independent manner. These results may add important information to the field of inflammation and potentially lead to novel anti-inflammatory agents targeting the production of NETs.Keywords: Carrageenan r Myeloperoxidase r Neutrophil Elastase r Neutrophil Extracellular Traps r Neutrophils Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNeutrophils are the first cells involved in defense against pathogens and present a mechanism called neutrophil extracellular traps (NETs), which are extracellular structures able to trap and kill pathogens [1,2]. NETs are fibers made of Correspondence: Prof. Márcio V. F. Donadio e-mail: mdonadio@pucrs.br decondensed chromatin (histones and DNA) decorated with antimicrobial proteolytic enzymes present in the granules of neutrophils (such as neutrophil elastase (NE) and myeloperoxidase (MPO)) [3] and other nuclear components, all apparently involved in its mechanism of action [4]. There are a variety of stimuli yet described in the literature including proteins, bacteria, fungi, viruses, and cytokines capable of inducing NETs release [1,[5][6][7]. NETs are present in a plenty of in vivo inflammatory conditions, such as endometriosis [8] importance of exploring inflammatory stimuli involved in NETs formation.Carrageenan is a sulfated polysaccharide extracted from Chondrus crispus, a marine algae, used for decades in research for its potential to induce inflammation [13]. Also, carrageenan is widely used by the food industry as a gelling agent [13]. Due to the potential induction of inflammation, carrageenan is often used as a model of pleurisy [14,15], peritonitis [16,17], and edema [17,18] in experimental animals. The injection of carrageenan triggers an acute inflammation associated with hyperalgesy, which is characterized by edema and an exacerbated response to thermal and mechanical stimuli [13]. Bhattacharyya and colleagues found that carrageenan-induced inflammation in vitro in human colonocytes occurs through activation of Tolllike receptor...

The aim of this study is to evaluate the response to an inflammatory stimulus in mice exposed to LPS-induced neonatal stress at different ages and sexes. Balb/c mice were submitted to intraperitoneal injections on postnatal days 3 and 10 with lipopolysaccharide (nLPS) or saline solution (nSal). At 21 or 60 days, either saline solution was injected or an inflammatory stimulus was induced by the injection of 1% carrageenan. Inflammatory cytokines, reactive oxygen species, and neutrophil extracellular traps (NETs) production were measured in peritoneal fluid. LPS-induced neonatal stress can reduce inflammatory cytokines in males and females. An increase in NETs production was observed when 60 day nLPS animals were compared to 21 day mice in both sexes. The ROS production was not affected by neonatal stress. The results shown here indicate that LPS-induced neonatal stress can alter cytokine production in response to inflammatory stimuli at different ages, in a sex-dependent effect. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 600-613, 2016.

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