Role of neutrophils in equine asthma

2018 ◽  
Vol 19 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Benjamin Uberti ◽  
Gabriel Morán
Keyword(s):  
Tissue Injury ◽  
Oxygen Species ◽  
Cytokine Release ◽  
Extracellular Traps ◽  
Early Responder ◽  
Inflammatory Processes ◽  
Equine Asthma ◽  
Pulmonary Remodeling ◽  
Neutrophil Survival

AbstractNeutrophilic bronchiolitis is the primary lesion in asthma-affected horses. Neutrophils are key actors in host defense, migrating toward sites of inflammation and infection, where they act as early responder cells toward external insults. However, neutrophils can also mediate tissue damage in various non-infectious inflammatory processes. Within the airways, these cells likely contribute to bronchoconstriction, mucus hypersecretion, and pulmonary remodeling by releasing pro-inflammatory mediators, including the cytokines interleukin (IL)-8 and IL-17, neutrophil elastase, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). The mechanisms that regulate neutrophil functions in the tissues are complex and incompletely understood. Therefore, the inflammatory activity of neutrophils must be regulated with exquisite precision and timing, a task achieved through a complex network of mechanisms that regulates neutrophil survival. The discovery and development of compounds that can help regulate ROS, NET formation, cytokine release, and clearance would be highly beneficial in the design of therapies for this disease in horses. In this review, neutrophil functions during inflammation will be discussed followed by a discussion of their contribution to airway tissue injury in equine asthma.

scholarly journals Paraoxonases Activities and Polymorphisms in Elderly and Old-Age Diseases: An Overview

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 118 ◽  
Author(s):  
Débora Levy ◽  
Cadiele Oliana Reichert ◽  
Sérgio Paulo Bydlowski
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Tissue Injury ◽  
Density Lipoprotein ◽  
The Elderly ◽  
Chromosome 7 ◽  
Oxygen Species ◽  
Structural Homology ◽  
Inflammatory Processes

Aging is defined as the accumulation of progressive organ dysfunction. There is much evidence linking the involvement of oxidative stress in the pathogenesis of aging. With increasing age, susceptibility to the development of diseases related to lipid peroxidation and tissue injury increases, due to chronic inflammatory processes, and production of reactive oxygen species (ROS) and free radicals. The paraoxonase (PON) gene family is composed of three members (PON1, PON2, PON3) that share considerable structural homology and are located adjacently on chromosome 7 in humans. The most studied member product is PON1, a protein associated with high-density lipoprotein with paraoxonase/esterase activity. Nevertheless, all the three proteins prevent oxidative stress. The major aim of this review is to highlight the importance of the role of PON enzymes in the aging process, and in the development of the main diseases present in the elderly: cardiovascular disease, diabetes mellitus, neurodegenerative diseases, and cancer.

scholarly journals NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sunil Joshi ◽  
Ammon B. Peck ◽  
Saeed R. Khan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tissue Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Renal Tissue ◽  
Oxygen Species ◽  
Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

scholarly journals Academic-industry partnerships in addressing nutrition – [Infection-immunity-inflammation] interactions

2007 ◽  
Vol 98 (S1) ◽  
pp. S17-S23 ◽  
Author(s):  
Ricardo Uauy
Keyword(s):  
Cell Injury ◽  
Tissue Injury ◽  
Infectious Agent ◽  
Nutritional Supplement ◽  
Novel Foods ◽  
Protein Energy ◽  
Toxic Damage ◽  
Inflammatory Processes ◽  
The Impact

The interaction between nutrition and infection is a key determinant of human health. Traditionally the interaction has centered on the role of nutrients in defining host defenses and the impact of infection in defining nutritional needs and status. Over the past decades the interaction has expanded its scope to encompass the role of specific nutrients in defining acquired immune function, in the modulation of inflammatory processes and on the virulence of the infectious agent itself. More recently the role of micronutrients and fatty acids on the response of cells and tissues to hypoxic and toxic damage has been recognized suggesting a fourth dimension to the interaction. The list of nutrients affecting infection, immunity, inflammation and cell injury has expanded from traditional protein-energy supply to several vitamins, multiple minerals and more recently specific lipid components of the diet. The promise of nutrition in the defense against infection, inflammation and tissue injury has spawned a thriving pharma-nutritional supplement industry and the development of novel foods that require appropriate evaluation of efficacy, safety and effectiveness relative to costs. Academics need to aware of the ethics and the pitfalls in the interaction with industry; conversely industry has to define its role in the process of bringing new knowledge to useful products. The process needs to be interactive, transparent and clearly place public interest above all other considerations.

Proinflammatory role of neutrophil extracellular traps in abdominal sepsis

2014 ◽  
Vol 307 (7) ◽  
pp. L586-L596 ◽  
Author(s):  
Lingtao Luo ◽  
Su Zhang ◽  
Yongzhi Wang ◽  
Milladur Rahman ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Lung Injury ◽  
Peritoneal Cavity ◽  
Tissue Injury ◽  
Cecal Ligation ◽  
Neutrophil Extracellular Traps ◽  
Abdominal Sepsis ◽  
Extracellular Dna ◽  
Extracellular Traps ◽  
Proinflammatory Role

Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with recombinant human (rh)DNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green, and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity, and lung. Blood, peritoneal fluid, and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury, as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in plasma, peritoneal cavity, and lung. Administration of rhDNAse not only eliminated NET formation in plasma, peritoneal cavity, and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6, and high-mobility group box 1 (HMGB1) in plasma, as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α, and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of proinflammatory compounds in abdominal sepsis. Thus we conclude that NETs exert a proinflammatory role in septic lung injury.

scholarly journals Overexpression of ATG5 Gene Makes Granulocyte-Like HL-60 Susceptible to Release Reactive Oxygen Species

2020 ◽  
Vol 21 (15) ◽  
pp. 5194 ◽  
Author(s):  
Agnieszka Mroczek ◽  
Adrianna Cieloch ◽  
Aneta Manda-Handzlik ◽  
Weronika Kuźmicka ◽  
Angelika Muchowicz ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Fluorescent Microscopy ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Extracellular Traps ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Proliferation And Apoptosis

Neutrophils represent the first line of defense against pathogens using various strategies, such as phagocytosis, production of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) formation. Recently, an autophagy-independent role of autophagy related (ATG) gene 5 in immune cells, including neutrophils, was emphasized. Our aim was to investigate the role of ATG5 protein in neutrophils’ antimicrobial functions, proliferation and apoptosis. To this end, we used genetically modified human promyelocytic leukemia (HL-60) cells overexpressing ATG5, differentiated toward granulocyte-like cells with all-trans retinoic acid (ATRA) and dimethylformamide. The level of differentiation, phagocytosis, proliferation and apoptosis were determined by flow cytometry. ROS production and NETs release was assessed by fluorometry and fluorescent microscopy. ATG5 gene expression was evaluated by real-time PCR, whereas the protein level of ATG5 and LC3-II was determined by Western blot. We did not observe the induction of autophagy in differentiated HL-60 cells overexpressing ATG5. The increased expression of ATG5 affects the differentiation of HL-60 cells with ATRA, ROS production and phagocytosis. However, we did not detect changes in NETs release. Moreover, ATG5 protects differentiated HL-60 cells from apoptosis but does not cause changes in proliferation rate.

scholarly journals Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 31
Author(s):  
María Amparo Blanch-Ruiz ◽  
Raquel Ortega-Luna ◽  
Guillermo Gómez-García ◽  
Maria Ángeles Martínez-Cuesta ◽  
Ángeles Álvarez
Keyword(s):  
Effective Treatment ◽  
Inflammatory Markers ◽  
Distress Syndrome ◽  
Neutrophil Extracellular Traps ◽  
Multiple Organ ◽  
Oxygen Species ◽  
Albumin Ratio ◽  
Extracellular Traps ◽  
Severity Of The Disease

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in a pandemic with over 270 million confirmed cases and 5.3 million deaths worldwide. In some cases, the infection leads to acute respiratory distress syndrome (ARDS), which is triggered by a cytokine storm and multiple organ failure. Clinical hematological, biochemical, coagulation, and inflammatory markers, such as interleukins, are associated with COVID-19 disease progression. In this regard, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-albumin ratio (NAR), have emerged as promising biomarkers of disease severity and progression. In the pathophysiology of ARDS, the inflammatory environment induces neutrophil influx and activation in the lungs, promoting the release of cytokines, proteases, reactive oxygen species (ROS), and, eventually, neutrophil extracellular traps (NETs). NETs components, such as DNA, histones, myeloperoxidase, and elastase, may exert cytotoxic activity and alveolar damage. Thus, NETs have also been described as potential biomarkers of COVID-19 prognosis. Several studies have demonstrated that NETs are induced in COVID-19 patients, and that the highest levels of NETs are found in critical ones, therefore highlighting a correlation between NETs and severity of the disease. Knowledge of NETs signaling pathways, and the targeting of points of NETs release, could help to develop an effective treatment for COVID-19, and specifically for severe cases, which would help to manage the pandemic.

scholarly journals The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis and Complications of Malignant Diseases

2020 ◽  
Author(s):  
Sheniz Yuzeir ◽  
Liana Gercheva
Keyword(s):  
Current Knowledge ◽  
Tumour Progression ◽  
Neutrophil Extracellular Traps ◽  
Malignant Diseases ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Inflammatory Processes ◽  
Thrombotic Complications ◽  
Clinically Significant

It was recently proved that neutrophils and platelets are active participants in some inflammatory processes as well as a number of pathological conditions, including neoplastic diseases and thrombosis. It has been found that circulating neutrophils actively affect the mechanisms of tumour genesis, and along with platelets, act as independent regulators of different complications in infectious and malignant diseases. A few years ago, it was found that neutrophils have the ability to release extracellular traps (called neutrophil extracellular traps or NETs). Thus, neutrophils use both intracellular and extracellular mechanisms to limit inflammatory complications. Several recent studies confirmed that NETs increase considerably in malignant diseases, demonstrating that tumour-induced NETosis is a clinically significant process. It is recognised as an element of tumour biology, as it participates in tumour progression and angiogenesis. Neutrophils and the NETs released from them are stimulators of thrombotic processes in physiological and pathological conditions. Several reports demonstrate the connection between NETs and thrombosis. The presence of NETosis serves as a potential risk factor for thrombotic complications in malignant diseases. This chapter summarises the current knowledge of NETosis and the mechanisms that lead to the formation of NETs, including the role of circulating platelet–neutrophil complexes as regulators of tumour-induced NETosis in malignant diseases.

scholarly journals Cathelicidin – Its Structure, Function and the Role in Autoimmune Diseases

2014 ◽  
Vol 4 (2) ◽  
pp. 83-96 ◽  
Author(s):  
Magdalena Polcyn-Adamczak ◽  
Zofia I. Niemir
Keyword(s):  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Helical Structure ◽  
Threshold Concentration ◽  
Amino Acid Residues ◽  
Phospholipid Membrane ◽  
Gram Positive Bacteria ◽  
Extracellular Traps ◽  
Inflammatory Processes

Summary Antimicrobial peptides are widely distributed in nature, and they are found in both Prokaryotes and Eukaryotes. Due to their characteristics, structure, functions and mode of action, they are divided into several groups. The only member of this family occurring in humans is cathelicidin - LL-37. It is produced as an inactive hCAP18 propeptide. The propeptide’s C-terminal fragment becomes a mature peptide subsequently to its enzymatic cleavage. LL-37 contains 37-amino acid residues, folds into α-helical structure and has amphipathic properties. Cathelicidin mechanism of action consists in the binding of LL-37 to the bacterial phospholipid membrane until a threshold concentration is reached, followed by the cytoplasm disintegration and leakage, and, finally, cell death. The peptide is expressed in several cells, for instance in the epithelial cells of testis, keratinocytes in the skin, leukocytes, monocytes, neutrophils, as well as T, B, and NK cells. Cathelicidin is a multifunctional molecule. It can serve as a mediator in inflammatory processes and/or as a natural antibiotic against Gram-negative and Gram-positive bacteria, viruses, and fungi. It is chemotactic for mononuclear cells, neutrophils, eosinophils, mast cells and T lymphocytes. LL-37 induces expression of chemokines, neutralises endotoxins, stimulates angiogenesis and apoptosis, as well as it boosts wound healing. Recent data have revealed an important role of LL-37 in the pathogenesis of systemic lupus erythematosus due to an impaired degradation of components in the neutrophil extracellular traps

Role of the perforin/granzyme cell death pathway ind-Gal/LPS-induced inflammatory liver injury

2009 ◽  
Vol 296 (5) ◽  
pp. G1069-G1076 ◽  
Author(s):  
Angela Kuhla ◽  
Christian Eipel ◽  
Kerstin Abshagen ◽  
Nikolai Siebert ◽  
Michael D. Menger ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Failure ◽  
Tissue Damage ◽  
Tissue Injury ◽  
Cytokine Release ◽  
Lps Challenge ◽  
Cell Death Pathway ◽  
Tnf Α ◽  
Hepatocellular Apoptosis

Cytotoxic T lymphocytes and their granule components, such as perforin and granzyme, play an important role in the defense of hepatic infections caused by different pathogens. Moreover, it has been shown in vitro that hepatocytes can initiate cell death via a perforin-dependent mechanism. Although it is well known that hepatocellular apoptosis in d-galactosamine/lipopolysaccharide (d-Gal/LPS)-associated liver failure is mediated by TNF-α-dependent Fas/FasL cytotoxicity, there is no information on the role of perforin-mediated mechanisms in vivo. Therefore, we studied whether the cytolytic perforin/granzyme pathway contributes to the d-Gal/LPS-associated hepatotoxicity. Perforin knockout (Pko) mice showed significantly higher hepatic TNF-α and IL-6 mRNA expression as well as plasma TNF-α and IL-6 concentrations within the first hour upon d-Gal/LPS challenge compared with perforin wild-type (Pwt) mice. At 6 h upon d-Gal/LPS challenge, Pko mice further presented with higher transaminase release and onconecrotic tissue damage, whereas hepatocellular apoptosis and caspase-3 cleavage remained unaffected by the perforin deficiency. Pretreatment with a recombinant human TNF-α receptor fusion protein attenuated necrotic and apoptotic tissue damage and reduced plasma transaminase activities as well as cytokine release, thereby preventing acute liver failure in Pko mice as effectively as in Pwt mice. These data do not only confirm the significance of TNF-α as distal mediator of hepatic injury in this model but simultaneously reveal a contribution of a perforin-dependent immunoregulation, limiting the d-Gal/LPS-induced overwhelming cytokine release and onconecrotic tissue injury.

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