Research

15 pages, 3047 KiB

Open AccessArticle

The GAG-Binding Peptide MIG30 Protects against Liver Ischemia-Reperfusion in Mice

by Thiago Henrique Caldeira Oliveira, Vincent Vanheule, Sofie Vandendriessche, Fariba Poosti, Mauro Martins Teixeira, Paul Proost, Mieke Gouwy and Pedro Elias Marques

Int. J. Mol. Sci. 2022, 23(17), 9715; https://doi.org/10.3390/ijms23179715 - 26 Aug 2022

Cited by 1 | Viewed by 1577

Abstract

Ischemia-reperfusion injury (IRI) drives graft rejection and is the main cause of mortality after liver transplantation. During IRI, an intense inflammatory response marked by chemokine production and neutrophil recruitment occurs. However, few strategies are available to restrain this excessive response. Here, we aimed [...] Read more.

Ischemia-reperfusion injury (IRI) drives graft rejection and is the main cause of mortality after liver transplantation. During IRI, an intense inflammatory response marked by chemokine production and neutrophil recruitment occurs. However, few strategies are available to restrain this excessive response. Here, we aimed to interfere with chemokine function during IRI in order to disrupt neutrophil recruitment to the injured liver. For this, we utilized a potent glycosaminoglycan (GAG)-binding peptide containing the 30 C-terminal amino acids of CXCL9 (MIG30) that is able to inhibit the binding of chemokines to GAGs in vitro. We observed that mice subjected to IRI and treated with MIG30 presented significantly lower liver injury and dysfunction as compared to vehicle-treated mice. Moreover, the levels of chemokines CXCL1, CXCL2 and CXCL6 and of proinflammatory cytokines TNF-α and IL-6 were significantly reduced in MIG30-treated mice. These events were associated with a marked inhibition of neutrophil recruitment to the liver during IRI. Lastly, we observed that MIG30 is unable to affect leukocytes directly nor to alter the stimulation by either CXCL8 or lipopolysaccharide (LPS), suggesting that its protective properties derive from its ability to inhibit chemokine activity in vivo. We conclude that MIG30 holds promise as a strategy to treat liver IRI and inflammation. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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Review

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17 pages, 1853 KiB

Open AccessReview

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia

by Alexandru Leonard Alexa, Sergiu Sargarovschi and Daniela Ionescu

Int. J. Mol. Sci. 2024, 25(7), 4033; https://doi.org/10.3390/ijms25074033 - 04 Apr 2024

Viewed by 503

Abstract

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied [...] Read more.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions’; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils’ functions and their potential influence on perioperative outcomes. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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16 pages, 4343 KiB

Open AccessReview

The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies

by Agata Walulik, Kinga Łysak, Michał Błaszkiewicz, Ignacy Górecki and Krzysztof Gomułka

Int. J. Mol. Sci. 2023, 24(24), 17217; https://doi.org/10.3390/ijms242417217 - 07 Dec 2023

Viewed by 1018

Abstract

Recent years have brought progress in understanding the role of the neutrophil, dispelling the dogma of homogeneous cells mainly involved in the prime defence against pathogens, shedding light on their pathogenic role in inflammatory diseases and on the importance of antineutrophil-cytoplasmic antibodies’ pathogenic [...] Read more.

Recent years have brought progress in understanding the role of the neutrophil, dispelling the dogma of homogeneous cells mainly involved in the prime defence against pathogens, shedding light on their pathogenic role in inflammatory diseases and on the importance of antineutrophil-cytoplasmic antibodies’ pathogenic role in ANCA-associated vasculitides vasculitis (AAV). Myeloperoxidase (MPO) and proteinase 3 (PR3) expressed in neutrophil granulocytes are the most common targets for ANCAs and contribute to the formation of MPO-ANCAs and PR3-ANCAs which, released to the bloodstream, become an excellent diagnostic tool for AAV. In this study, we focus on increasing the clinical and experimental evidence that supports the pathogenic role of ANCAs in AAV. Additionally, we discuss the diagnostic utility of ANCAs for disease activity and prognosis in AAV. Understanding the central role of ANCAs in AAV is crucial for advancing our knowledge of these complex disorders and developing targeted therapeutic strategies in the era of personalized medicine. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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21 pages, 1372 KiB

Open AccessReview

Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances

by Md. Monirul Islam and Naoshi Takeyama

Int. J. Mol. Sci. 2023, 24(21), 15805; https://doi.org/10.3390/ijms242115805 - 31 Oct 2023

Cited by 4 | Viewed by 2140

Abstract

Neutrophils are the principal trouper of the innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture [...] Read more.

Neutrophils are the principal trouper of the innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host’s protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including the promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, and cancer diseases, and the list is increasing gradually. In this review, we summarize the NET-mediated pathophysiology of different diseases and focus on some updated potential therapeutic approaches against NETs. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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16 pages, 918 KiB

Open AccessReview

Neurotrophins: Expression of Brain–Lung Axis Development

by Sara Manti, Federica Xerra, Giulia Spoto, Ambra Butera, Eloisa Gitto, Gabriella Di Rosa and Antonio Gennaro Nicotera

Int. J. Mol. Sci. 2023, 24(8), 7089; https://doi.org/10.3390/ijms24087089 - 11 Apr 2023

Cited by 6 | Viewed by 2000

Abstract

Neurotrophins (NTs) are a group of soluble growth factors with analogous structures and functions, identified initially as critical mediators of neuronal survival during development. Recently, the relevance of NTs has been confirmed by emerging clinical data showing that impaired NTs levels and functions [...] Read more.

Neurotrophins (NTs) are a group of soluble growth factors with analogous structures and functions, identified initially as critical mediators of neuronal survival during development. Recently, the relevance of NTs has been confirmed by emerging clinical data showing that impaired NTs levels and functions are involved in the onset of neurological and pulmonary diseases. The alteration in NTs expression at the central and peripheral nervous system has been linked to neurodevelopmental disorders with an early onset and severe clinical manifestations, often named "synaptopathies" because of structural and functional synaptic plasticity abnormalities. NTs appear to be also involved in the physiology and pathophysiology of several airway diseases, neonatal lung diseases, allergic and inflammatory diseases, lung fibrosis, and even lung cancer. Moreover, they have also been detected in other peripheral tissues, including immune cells, epithelium, smooth muscle, fibroblasts, and vascular endothelium. This review aims to provide a comprehensive description of the NTs as important physiological and pathophysiological players in brain and lung development. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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16 pages, 1592 KiB

Open AccessReview

Neutrophils in Health and Disease: From Receptor Sensing to Inflammasome Activation

by Agnieszka Iwaniuk and Ewa Jablonska

Int. J. Mol. Sci. 2023, 24(7), 6340; https://doi.org/10.3390/ijms24076340 - 28 Mar 2023

Cited by 2 | Viewed by 1621

Abstract

Neutrophils—polymorphonuclear cells (PMNs) are the cells of the initial immune response and make up the majority of leukocytes in the peripheral blood. After activation, these cells modify their functional status to meet the needs at the site of action or according to the [...] Read more.

Neutrophils—polymorphonuclear cells (PMNs) are the cells of the initial immune response and make up the majority of leukocytes in the peripheral blood. After activation, these cells modify their functional status to meet the needs at the site of action or according to the agent causing injury. They receive signals from their surroundings and “plan” the course of the response in both temporal and spatial contexts. PMNs dispose of intracellular signaling pathways that allow them to perform a wide range of functions associated with the development of inflammatory processes. In addition to these cells, some protein complexes, known as inflammasomes, also have a special role in the development and maintenance of inflammation. These complexes participate in the proteolytic activation of key pro-inflammatory cytokines, such as IL-1β and IL-18. In recent years, there has been significant progress in the understanding of the structure and molecular mechanisms behind the activation of inflammasomes and their participation in the pathogenesis of numerous diseases. The available reports focus primarily on macrophages and dendritic cells. According to the literature, the activation of inflammasomes in neutrophils and the associated death type—pyroptosis—is regulated in a different manner than in other cells. The present work is a review of the latest reports concerning the course of inflammasome activation and inflammatory cytokine secretion in response to pathogens in neutrophils, as well as the role of these mechanisms in the pathogenesis of selected diseases. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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17 pages, 933 KiB

Open AccessReview

The Role of Neutrophils in Spondyloarthritis: A Journey across the Spectrum of Disease Manifestations

by Lavinia Agra Coletto, Chiara Rizzo, Giuliana Guggino, Roberto Caporali, Stefano Alivernini and Maria Antonietta D’Agostino

Int. J. Mol. Sci. 2023, 24(4), 4108; https://doi.org/10.3390/ijms24044108 - 18 Feb 2023

Cited by 4 | Viewed by 2507

Abstract

Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells [...] Read more.

Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells crucial in orchestrating the pro-inflammatory response, both at systemic and tissue levels. It has been suggested they act as key players along multiple stages of disease trajectory fueling type 3 immunity, with a significant impact in the initiation and amplification of inflammation as well as in structural damage occurrence, typical of long-standing disease. The aim of our review is to focus on neutrophils’ role within the spectrum of SpA, dissecting their functions and abnormalities in each of the relevant disease domains to understand their rising appeal as potential biomarkers and therapeutic targets. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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42 pages, 4706 KiB

Open AccessReview

From Co-Infections to Autoimmune Disease via Hyperactivated Innate Immunity: COVID-19 Autoimmune Coagulopathies, Autoimmune Myocarditis and Multisystem Inflammatory Syndrome in Children

by Robert Root-Bernstein

Int. J. Mol. Sci. 2023, 24(3), 3001; https://doi.org/10.3390/ijms24033001 - 03 Feb 2023

Cited by 12 | Viewed by 2935

Abstract

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two of many measures of increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis and multisystem inflammatory syndrome in children (MIS-C). This paper integrates currently disparate measures of [...] Read more.

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two of many measures of increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis and multisystem inflammatory syndrome in children (MIS-C). This paper integrates currently disparate measures of innate hyperactivation in severe COVID-19 and its autoimmune complications, and relates these to SARS-CoV-2 activation of innate immunity. Aggregated data include activation of Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) receptors, NOD leucine-rich repeat and pyrin-domain-containing receptors (NLRPs), retinoic acid-inducible gene I (RIG-I) and melanoma-differentiation-associated gene 5 (MDA-5). SARS-CoV-2 mainly activates the virus-associated innate receptors TLR3, TLR7, TLR8, NLRP3, RIG-1 and MDA-5. Severe COVID-19, however, is characterized by additional activation of TLR1, TLR2, TLR4, TLR5, TLR6, NOD1 and NOD2, which are primarily responsive to bacterial antigens. The innate activation patterns in autoimmune coagulopathies, myocarditis and Kawasaki disease, or MIS-C, mimic those of severe COVID-19 rather than SARS-CoV-2 alone suggesting that autoimmunity follows combined SARS-CoV-2-bacterial infections. Viral and bacterial receptors are known to synergize to produce the increased inflammation required to support autoimmune disease pathology. Additional studies demonstrate that anti-bacterial antibodies are also required to account for known autoantigen targets in COVID-19 autoimmune complications. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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Other

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11 pages, 1661 KiB

Open AccessPerspective

Can Neutrophils Prevent Nosocomial Pneumonia after Serious Injury?

by Kristína Macáková, Elzbieta Kaczmarek and Kiyoshi Itagaki

Int. J. Mol. Sci. 2023, 24(8), 7627; https://doi.org/10.3390/ijms24087627 - 21 Apr 2023

Cited by 1 | Viewed by 1240

Abstract

Nosocomial pneumonia is a leading cause of critical illness and mortality among seriously injured trauma patients. However, the link between injury and the development of nosocomial pneumonia is still not well recognized. Our work strongly suggests that mitochondrial damage-associated molecular patterns (mtDAMPs), especially [...] Read more.

Nosocomial pneumonia is a leading cause of critical illness and mortality among seriously injured trauma patients. However, the link between injury and the development of nosocomial pneumonia is still not well recognized. Our work strongly suggests that mitochondrial damage-associated molecular patterns (mtDAMPs), especially mitochondrial formyl peptides (mtFPs) released by tissue injury, play a significant role in developing nosocomial pneumonia after a serious injury. Polymorphonuclear leukocytes (neutrophils, PMN) migrate toward the injury site by detecting mtFPs through formyl peptide receptor 1 (FPR1) to fight/contain bacterial infection and clean up debris. Activation of FPR1 by mtFPs enables PMN to reach the injury site; however, at the same time it leads to homo- and heterologous desensitization/internalization of chemokine receptors. Thus, PMN are not responsive to secondary infections, including those from bacteria-infected lungs. This may enable a progression of bacterial growth in the lungs and nosocomial pneumonia. We propose that the intratracheal application of exogenously isolated PMN may prevent pneumonia coupled with a serious injury. Full article

(This article belongs to the Special Issue The Role and Characterization of Neutrophils in Human Diseases)

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