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Neutrophil in Cell Biology and Diseases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 20848

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Guest Editor
Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1A, 119992 Moscow, Russia
Interests: free radicals; antioxidants; reactive oxygen species; free radical scavengers; oxidative stress biomarkers; redox signaling; inflammatory biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neutrophils, which are the most abundant circulating white blood cells in human, are the first leukocytes recruited to infection sites. They are well known for their host defense activity; however, the physiological roles of neutrophils are not restricted to infectious diseases. Recent evidence has grown, suggesting the novel physiological roles of neutrophils in various conditions from steady state to various diseases, including infectious diseases, sterile inflammatory diseases, autoimmune diseases, and cancer. The unique niche of neutrophils in disease conditions comes from their functions resulting from activation, such as phagocytosis, generation of reactive oxygen species, degranulation, and neutrophil extracellular traps formation.

Furthermore, accumulating evidence demonstrates the existence of neutrophil heterogeneity in diverse pathophysiological conditions, similar to other myeloid lineage cells, including monocytes and macrophages. Knowledge of the newly identified neutrophil population greatly contributes to our understanding of the functional roles of neutrophils in various pathological conditions.

This Special Issue is focused on the new molecular mechanisms involved in the regulation of neutrophil activity, the novel physiological role of neutrophils in diseases, as well as the heterogeneity of neutrophils in diverse diseases. Manuscripts that provide such information will be welcomed.

Dr. Elena Mikhalchik
Guest Editor

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Keywords

  • neutrophil
  • neutrocytes
  • host defense
  • neutrophil extracellular traps
  • neutrophil heterogeneity

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Published Papers (14 papers)

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15 pages, 5508 KiB  
Article
The CD177 c.1291A Allele Leads to a Loss of Membrane Expression and Mimics a CD177-Null Phenotype
by Annalena Traum, Stefanie Jehle, Yannick Waxmann, Anne-Sophie Litmeyer, Heike Berghöfer, Gregor Bein, Reinhard Dammann, Alexander Perniss, Monika Burg-Roderfeld, Ulrich J. Sachs and Behnaz Bayat
Int. J. Mol. Sci. 2024, 25(5), 2877; https://doi.org/10.3390/ijms25052877 - 01 Mar 2024
Viewed by 513
Abstract
CD177 is a glycosyl phosphatidyl inositol (GPI)-linked, neutrophil-specific glycoprotein that in 3–5% of normal individuals is absent from all neutrophils. The molecular mechanism behind the absence of CD177 has not been unravelled completely. Here, we analyse the impact of the recently described CD177 [...] Read more.
CD177 is a glycosyl phosphatidyl inositol (GPI)-linked, neutrophil-specific glycoprotein that in 3–5% of normal individuals is absent from all neutrophils. The molecular mechanism behind the absence of CD177 has not been unravelled completely. Here, we analyse the impact of the recently described CD177 c.1291G>A variant on CD177 expression. Recombinant CD177 c.1291G>A was expressed in HEK293F cells and its expression on the cell surface, inside the cell, and in the culture supernatant was investigated. The CD177 c.1291G>A protein was characterised serologically and its interaction with proteinase 3 (PR3) was demonstrated by confocal laser scanning microscopy. Our experiments show that CD177 c.1291G>A does not interfere with CD177 protein biosynthesis but affects the membrane expression of CD177, leading to very low copy numbers of the protein on the cellular surface. The mutation does not interfere with the ability of the protein to bind PR3 or human polyclonal antibodies against wild-type CD177. Carriers of the c.1291G>A allele are supposed to be phenotyped as CD177-negative, but the protein is present in soluble form. The presence of CD177 c.1291A leads to the production of an unstable CD177 protein and an apparent “CD177-null” phenotype. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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11 pages, 2262 KiB  
Article
Inhibiting Neutrophil Extracellular Traps Protects against Ultraviolet B-Induced Skin Damage: Effects of Hochu-ekki-to and DNase I
by Issei Inaba, Keiichi Hiramoto, Yurika Yamate, Akihiro Morita, Tomonari Tsutsumi, Hiroyuki Yasuda and Eisuke F. Sato
Int. J. Mol. Sci. 2024, 25(3), 1723; https://doi.org/10.3390/ijms25031723 - 31 Jan 2024
Viewed by 769
Abstract
UV-B radiation induces sunburn, and neutrophils are pivotal in this inflammation. In this study, we examined the potential involvement of neutrophil extracellular traps (NETs) in ultraviolet B (UVB)-induced skin inflammation, correlating the skin inflammation-mitigating effects of Hochu-ekki-to on UV-B irradiation and NETs. To [...] Read more.
UV-B radiation induces sunburn, and neutrophils are pivotal in this inflammation. In this study, we examined the potential involvement of neutrophil extracellular traps (NETs) in ultraviolet B (UVB)-induced skin inflammation, correlating the skin inflammation-mitigating effects of Hochu-ekki-to on UV-B irradiation and NETs. To elucidate NET distribution in the dorsal skin, male ICR mice, exposed to UVB irradiation, were immunohistologically analyzed to detect citrullinated histone H3 (citH3) and peptidylarginine deiminase 4 (PAD4). Reactive oxygen species (ROS) production in the bloodstream was analyzed. To establish the involvement of NET-released DNA in this inflammatory response, mice were UV-B irradiated following the intraperitoneal administration of DNase I. In vitro experiments were performed to scrutinize the impact of Hochu-ekki-to on A23187-induced NETs in neutrophil-like HL-60 cells. UV-B irradiation induced dorsal skin inflammation, coinciding with a significant increase in citH3 and PAD4 expression. Administration of DNase I attenuated UV-B-induced skin inflammation, whereas Hochu-ekki-to administration considerably suppressed the inflammation, correlating with diminished levels of citH3 and PAD4 in the dorsal skin. UV-B irradiation conspicuously augmented ROS and hydrogen peroxide (H2O2) production in the blood. Hochu-ekki-to significantly inhibited ROS and H2O2 generation. In vitro experiments demonstrated that Hochu-ekki-to notably inhibited A23187-induced NETs in differentiated neutrophil-like cells. Hence, NETs have been implicated in UV-B-induced skin inflammation, and their inhibition reduces cutaneous inflammation. Additionally, Hochu-ekki-to mitigated skin inflammation by impeding neutrophil infiltration and NETs in the dorsal skin of mice. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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14 pages, 3534 KiB  
Article
Heterogeneity in Neutrophil Extracellular Traps from Healthy Human Subjects
by Margaret S. Collins, Michelle A. Imbrogno, Elizabeth J. Kopras, James A. Howard, Nanhua Zhang, Elizabeth L. Kramer and Kristin M. Hudock
Int. J. Mol. Sci. 2024, 25(1), 525; https://doi.org/10.3390/ijms25010525 - 30 Dec 2023
Viewed by 754
Abstract
Neutrophil extracellular traps (NETs), a key component of early defense against microbial infection, are also associated with tissue injury. NET composition has been reported to vary with some disease states, but the composition and variability of NETs across many healthy subjects provide a [...] Read more.
Neutrophil extracellular traps (NETs), a key component of early defense against microbial infection, are also associated with tissue injury. NET composition has been reported to vary with some disease states, but the composition and variability of NETs across many healthy subjects provide a critical comparison that has not been well investigated. We evaluated NETs from twelve healthy subjects of varying ages isolated from multiple blood draws over a three-and-one-half-year period to delineate the variability in extracellular DNA, protein, enzymatic activities, and susceptibility to protease inhibitors. We calculated correlations for NET constituents and loss of human bronchial epithelial barrier integrity, measured by transepithelial electrical resistance, after NET exposure. We found that although there was some variability within the same subject over time, the mean NET total DNA, dsDNA, protein, LDH, neutrophil elastase (NE), and proteinase 3 (PR3) in isolated NETs were consistent across subjects. NET serine protease activity varied considerably within the same donor from day to day. The mean NET cathepsin G and MPO were significantly different across donors. IL-8 > IL-1RA > G-CSF were the most abundant cytokines in NETs. There was no significant difference in the mean concentration or variability of IL-8, IL-1RA, G-CSF, IL-1α, IL-1β, or TNF-α in different subjects’ NETs. NET DNA concentration was correlated with increased NET neutrophil elastase activity and higher NET IL-1RA concentrations. The mean reduction in protease activity by protease inhibitors was significantly different across donors. NET DNA concentration correlated best with reductions in the barrier integrity of human bronchial epithelia. Defining NET concentration by DNA content correlates with other NET components and reductions in NET-driven epithelial barrier dysfunction, suggesting DNA is a reasonable surrogate measurement for these complex structures in healthy subjects. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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15 pages, 3339 KiB  
Article
Incorporation of Pectin into Vaterite Microparticles Prevented Effects of Adsorbed Mucin on Neutrophil Activation
by Elena V. Mikhalchik, Liliya N. Maltseva, Roxalana K. Firova, Marina A. Murina, Irina V. Gorudko, Daria V. Grigorieva, Viktor A. Ivanov, Ekaterina A. Obraztsova, Dmitry V. Klinov, Ekaterina V. Shmeleva, Sergey A. Gusev, Oleg M. Panasenko, Alexey V. Sokolov, Nikolay P. Gorbunov, Lyubov Y. Filatova and Nadezhda G. Balabushevich
Int. J. Mol. Sci. 2023, 24(21), 15927; https://doi.org/10.3390/ijms242115927 - 03 Nov 2023
Viewed by 780
Abstract
The application of vaterite microparticles for mucosal delivery depends on their interaction with mucin and immune cells. As we have shown previously, the binding of mucin onto particles enhances the generation of reactive oxygen species by neutrophils. The attenuation of the pro-oxidant effect [...] Read more.
The application of vaterite microparticles for mucosal delivery depends on their interaction with mucin and immune cells. As we have shown previously, the binding of mucin onto particles enhances the generation of reactive oxygen species by neutrophils. The attenuation of the pro-oxidant effect of the bound mucin through the modification of vaterite could improve its biocompatibility. Hybrid microparticles composed of vaterite and pectin (CCP) were prepared using co-precipitation. In comparison with vaterite (CC), they had a smaller diameter and pores, a greater surface area, and a negative zeta-potential. We aimed to study the cytotoxicity and mucin-dependent neutrophil-activating effect of CCP microparticles. The incorporated pectin did not influence the neutrophil damage according to a lactate dehydrogenase test. The difference in the CC- and CCP-elicited luminol or lucigenin chemiluminescence of neutrophils was insignificant, with no direct pro- or antioxidant effects from the incorporated pectin. Unlike soluble pectin, the CCP particles were ineffective at scavenging radicals in an ABAP–luminol test. The fluorescence of SYTOX Green demonstrated a CCP-stimulated formation of neutrophil extracellular traps (NETs). The pre-treatment of CC and CCP with mucin resulted in a 2.5-times-higher CL response of neutrophils to the CC-mucin than to the CCP-mucin. Thus, the incorporation of pectin into vaterite microspheres enabled an antioxidant effect to be reached when the neutrophils were activated by mucin-treated microparticles, presumably via exposed ligands. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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21 pages, 6157 KiB  
Article
Effect of Antioxidant Supplementation on NET Formation Induced by LPS In Vitro; the Roles of Vitamins E and C, Glutathione, and N-acetyl Cysteine
by Germán Muñoz-Sánchez, Lucila A. Godínez-Méndez, Mary Fafutis-Morris and Vidal Delgado-Rizo
Int. J. Mol. Sci. 2023, 24(17), 13162; https://doi.org/10.3390/ijms241713162 - 24 Aug 2023
Viewed by 895
Abstract
Neutrophil extracellular traps (NETs) require reactive oxygen species (ROS) to eliminate pathogens by inducing oxidative stress. However, this process can also cause tissue damage to the host. Neutrophils contain high concentrations of vitamin C (1.5 mM) compared to the bloodstream (0.1 mM), and [...] Read more.
Neutrophil extracellular traps (NETs) require reactive oxygen species (ROS) to eliminate pathogens by inducing oxidative stress. However, this process can also cause tissue damage to the host. Neutrophils contain high concentrations of vitamin C (1.5 mM) compared to the bloodstream (0.1 mM), and this antioxidant can interact with vitamin E and glutathione (GSH) inside the cell to maintain the redox balance. Previous studies have investigated the effect of vitamins E or C and N-acetyl cysteine (NAC) on NET formation, but the interactions of these molecules in neutrophils remain unknown. In this study, we investigated the effect of antioxidants alone and two combinations on NET formation and oxidative stress. Neutrophils were pre-loaded with GSH + NAC or vitamin E + vitamin C + GSH + NAC (termed ALL), and LPS-induced NET formation was assessed using fluorometry and immunofluorescence. Antioxidant effects were evaluated by measuring the total antioxidant capacity (TAC), GSH/GSSG ratio, ROS production, nitrite + nitrate levels, and lipid peroxidation. Our results showed that even low doses of antioxidants are capable of decreasing NETs. Furthermore, the combinations augmented TAC and GSH/GSSG ratio and decreased ROS, nitrites + nitrates, and malondialdehyde (MDA) levels in supplemented neutrophils in vitro. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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17 pages, 9869 KiB  
Article
Stages of NETosis Development upon Stimulation of Neutrophils with Activators of Different Types
by Vladimir Inozemtsev, Viktoria Sergunova, Nina Vorobjeva, Elena Kozlova, Ekaterina Sherstyukova, Snezhanna Lyapunova and Aleksandr Chernysh
Int. J. Mol. Sci. 2023, 24(15), 12355; https://doi.org/10.3390/ijms241512355 - 02 Aug 2023
Cited by 3 | Viewed by 1471
Abstract
Before NETs are released, the neutrophil undergoes structural changes. First, it flattens, accompanied by a change in cell shape and rearrangement of the cytoskeleton. Then, nuclear swelling begins, which ends with the ejection of NETs into the extracellular space. We used widefield and [...] Read more.
Before NETs are released, the neutrophil undergoes structural changes. First, it flattens, accompanied by a change in cell shape and rearrangement of the cytoskeleton. Then, nuclear swelling begins, which ends with the ejection of NETs into the extracellular space. We used widefield and confocal fluorescence microscopy to register morphological and structural changes in neutrophils during activation and NETosis. Different types of activators were used, such as NOX-dependent PMA and calcium ionophore A23187. The measurements were performed in a series of sequential stages. In the first stage (30 s after addition of activators and immediately after stimulation of neutrophils), the response of neutrophils to A23187 and PMA exposure was studied. Subsequently, the characteristics of neutrophils in different phases of activation were examined over a longer period of time (30, 60, 120, 180, and 240 min). The specific features of NETosis development were analyzed separately. During the first 30 s, neutrophils appeared to be heterogeneous in shape and structure of the actin cytoskeleton. Characteristic cell shapes included 30″ type 1 cells, similar in shape to the control, with F-actin concentrated in the center of the cytoplasm, and 30″ type 2 cells, which had flattened (spread) shapes with increased frontal dimensions and F-actin distributed throughout the cell. Later, the development of nuclear swelling, the corresponding changes in neutrophil membranes, and NET release into the extracellular space were evaluated. The conditions determining the initiation of chromatin ejection and two characteristic types of decondensed chromatin ejection were revealed. The results obtained contribute to a better understanding of the biophysical mechanisms of neutrophil activation and NETosis development. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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15 pages, 2608 KiB  
Article
In Vitro Evaluation of the Antiamoebic Activity of Kaempferol against Trophozoites of Entamoeba histolytica and in the Interactions of Amoebae with Hamster Neutrophils
by David Levaro-Loquio, Jesús Serrano-Luna, Maritza Velásquez-Torres, Germán Higuera-Martínez, Ivonne Maciel Arciniega-Martínez, Aldo Arturo Reséndiz-Albor, Nadia Mabel Pérez-Vielma and Judith Pacheco-Yépez
Int. J. Mol. Sci. 2023, 24(13), 11216; https://doi.org/10.3390/ijms241311216 - 07 Jul 2023
Viewed by 958
Abstract
Entamoeba histolytica (E. histolytica) is a parasite in humans that provokes amoebiasis. The most employed drug is metronidazole (MTZ); however, some studies have reported that this drug induces genotoxic effects. Therefore, it is necessary to explore new compounds without toxicity that [...] Read more.
Entamoeba histolytica (E. histolytica) is a parasite in humans that provokes amoebiasis. The most employed drug is metronidazole (MTZ); however, some studies have reported that this drug induces genotoxic effects. Therefore, it is necessary to explore new compounds without toxicity that can eliminate E. histolytica. Flavonoids are polyphenolic compounds that have demonstrated inhibition of growth and dysregulation of amoebic proteins. Despite the knowledge acquired to date, action mechanisms are not completely understood. The present work evaluates the effect of kaempferol against E. histolytica trophozoites and in the interactions with neutrophils from hamster, which is a susceptibility model. Our study demonstrated a significant reduction in the amoebic viability of trophozoites incubated with kaempferol at 150 μM for 90 min. The gene expression analysis showed a significant downregulation of Pr (peroxiredoxin), Rr (rubrerythrin), and TrxR (thioredoxin reductase). In interactions with amoebae and neutrophils for short times, we observed a reduction in ROS (reactive oxygen species), NO (nitric oxide), and MPO (myeloperoxidase) neutrophil activities. In conclusion, we confirmed that kaempferol is an effective drug against E. histolytica through the decrease in E. histolytica antioxidant enzyme expression and a regulator of several neutrophil mechanisms, such as MPO activity and the regulation of ROS and NO. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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25 pages, 2846 KiB  
Article
The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage
by Kristiana M. Amirova, Petya A. Dimitrova, Milena N. Leseva, Ivanka K. Koycheva, Albena T. Dinkova-Kostova and Milen I. Georgiev
Int. J. Mol. Sci. 2023, 24(10), 8775; https://doi.org/10.3390/ijms24108775 - 15 May 2023
Viewed by 1651
Abstract
The synthetic 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a potent activator of the erythroid 2-p45-derived factor 2, Nrf2, a leucine-zipper regulator of the antioxidant response. Herein, we investigated the effect of CDDO-Me on neutrophil function in a murine model of joint damage. Collagenase-induced [...] Read more.
The synthetic 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a potent activator of the erythroid 2-p45-derived factor 2, Nrf2, a leucine-zipper regulator of the antioxidant response. Herein, we investigated the effect of CDDO-Me on neutrophil function in a murine model of joint damage. Collagenase-induced osteoarthritis (CIOA) was initiated by the intra-articular injection of collagenase in the knee-joint cavity of Balb/c mice. CDDO-Me was administrated intra-articularly twice a week starting at day 7 post-CIOA, and its effect was evaluated at day 14. Neutrophils in blood and bone marrow (BM), cell apoptosis, necrosis, expression of C-X-C chemokine receptor 4 (CXCR4), beta-galactosidase (β-Gal), and Nrf2 levels were measured by flow cytometry. In vitro, CDDO-Me promoted cell survival, reduced cell necrosis, and increased Nrf2 levels by 1.6 times. It decreased surface CXCR4 expression and reduced the frequency of senescent β-Gal+CXCR4+ neutrophils by three times. In vivo, the degree of knee-joint damage in CIOA was correlated with upregulated CXCR4 on CD11b+ neutrophils. CDDO-Me improved the disease histological score, increased the levels of Nrf2, and downregulated surface CXCR4 on mature BM cells. Our data suggest that CDDO-Me may act as a potent regulator of neutrophil senescence during the progression of knee-joint damage. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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12 pages, 3723 KiB  
Article
Is the In Vitro Observed NETosis the Favored Physiological Death of Neutrophils or Mainly Induced by an Isolation Bias?
by Julia Rimboeck, Michael Gruber and Sigrid Wittmann
Int. J. Mol. Sci. 2023, 24(8), 7368; https://doi.org/10.3390/ijms24087368 - 17 Apr 2023
Cited by 1 | Viewed by 1135
Abstract
Centrifugation steps are regularly used for neutrophil isolation. Thereby, the influences of applied g-forces on the functionality of PMNs have hardly been analyzed and could consequently have been overlooked or led to biased results. We now hypothesize that blood PMNs—when gently isolated—can [...] Read more.
Centrifugation steps are regularly used for neutrophil isolation. Thereby, the influences of applied g-forces on the functionality of PMNs have hardly been analyzed and could consequently have been overlooked or led to biased results. We now hypothesize that blood PMNs—when gently isolated—can be long-lived cells and they physiologically become apoptotic rather than NETotic. Neutrophils were isolated from whole blood without centrifugation using a sedimentation enhancer (gelafundin). PMNs were analyzed via live-cell imaging for migratory activity and vitality condition by fluorescent staining. Native neutrophils showed still relevant migratory activity after more than 6 days ex vivo. The percentage of cells that were annexin V+ or PI+ increased successively with increasing ex vivo time. In addition, the characteristics of DAPI staining of gently isolated granulocytes differed markedly from those obtained by density gradient separation (DGS). We conclude that NETosis occurring after DGS is the consequence of applied g-forces and not a physiological phenomenon. Future studies on neutrophils should be performed with most native cells (applied g-time load as low as possible). Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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19 pages, 4494 KiB  
Article
Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase
by Michio Okamoto, Rei Mizuno, Kenji Kawada, Yoshiro Itatani, Yoshiyuki Kiyasu, Keita Hanada, Wataru Hirata, Yasuyo Nishikawa, Hideyuki Masui, Naoko Sugimoto, Takuya Tamura, Susumu Inamoto, Yoshiharu Sakai and Kazutaka Obama
Int. J. Mol. Sci. 2023, 24(2), 1118; https://doi.org/10.3390/ijms24021118 - 06 Jan 2023
Cited by 12 | Viewed by 2455
Abstract
Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs [...] Read more.
Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase–DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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Review

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28 pages, 684 KiB  
Review
Neutrophil Extracellular DNA Traps in Response to Infection or Inflammation, and the Roles of Platelet Interactions
by William A. Chen and Danilo S. Boskovic
Int. J. Mol. Sci. 2024, 25(5), 3025; https://doi.org/10.3390/ijms25053025 - 05 Mar 2024
Viewed by 743
Abstract
Neutrophils present the host’s first line of defense against bacterial infections. These immune effector cells are mobilized rapidly to destroy invading pathogens by (a) reactive oxygen species (ROS)-mediated oxidative bursts and (b) via phagocytosis. In addition, their antimicrobial service is capped via a [...] Read more.
Neutrophils present the host’s first line of defense against bacterial infections. These immune effector cells are mobilized rapidly to destroy invading pathogens by (a) reactive oxygen species (ROS)-mediated oxidative bursts and (b) via phagocytosis. In addition, their antimicrobial service is capped via a distinct cell death mechanism, by the release of their own decondensed nuclear DNA, supplemented with a variety of embedded proteins and enzymes. The extracellular DNA meshwork ensnares the pathogenic bacteria and neutralizes them. Such neutrophil extracellular DNA traps (NETs) have the potential to trigger a hemostatic response to pathogenic infections. The web-like chromatin serves as a prothrombotic scaffold for platelet adhesion and activation. What is less obvious is that platelets can also be involved during the initial release of NETs, forming heterotypic interactions with neutrophils and facilitating their responses to pathogens. Together, the platelet and neutrophil responses can effectively localize an infection until it is cleared. However, not all microbial infections are easily cleared. Certain pathogenic organisms may trigger dysregulated platelet–neutrophil interactions, with a potential to subsequently propagate thromboinflammatory processes. These may also include the release of some NETs. Therefore, in order to make rational intervention easier, further elucidation of platelet, neutrophil, and pathogen interactions is still needed. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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29 pages, 886 KiB  
Review
How Neutrophils Shape the Immune Response: Reassessing Their Multifaceted Role in Health and Disease
by Areez Shafqat, Jibran Ahmad Khan, Aghiad Yahya Alkachem, Homaira Sabur, Khaled Alkattan, Ahmed Yaqinuddin and Garwin Kim Sing
Int. J. Mol. Sci. 2023, 24(24), 17583; https://doi.org/10.3390/ijms242417583 - 18 Dec 2023
Cited by 3 | Viewed by 2647
Abstract
Neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation. Neutrophils are a heterogeneous group of immune cells from which are derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, [...] Read more.
Neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation. Neutrophils are a heterogeneous group of immune cells from which are derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, and alarmins that regulate the recruitment and phenotypes of neutrophils, macrophages, dendritic cells, T cells, and B cells. In addition, cytokine-stimulated neutrophils can express class II major histocompatibility complex and the internal machinery necessary for successful antigen presentation to memory CD4+ T cells. This may be relevant in the context of vaccine memory. Neutrophils thus emerge as orchestrators of immune responses that play a key role in determining the outcome of infections, vaccine efficacy, and chronic diseases like autoimmunity and cancer. This review aims to provide a synthesis of current evidence as regards the role of these functions of neutrophils in homeostasis and disease. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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19 pages, 1242 KiB  
Review
Neutrophils’ Contribution to Periodontitis and Periodontitis-Associated Cardiovascular Diseases
by Barbara Bassani, Martina Cucchiara, Andrea Butera, Omar Kayali, Alessandro Chiesa, Maria Teresa Palano, Francesca Olmeo, Matteo Gallazzi, Claudia Paola Bruna Dellavia, Lorenzo Mortara, Luca Parisi and Antonino Bruno
Int. J. Mol. Sci. 2023, 24(20), 15370; https://doi.org/10.3390/ijms242015370 - 19 Oct 2023
Cited by 3 | Viewed by 1977
Abstract
Neutrophils represent the primary defense against microbial threats playing a pivotal role in maintaining tissue homeostasis. This review examines the multifaceted involvement of neutrophils in periodontitis, a chronic inflammatory condition affecting the supporting structures of teeth summarizing the contribution of neutrophil dysfunction in [...] Read more.
Neutrophils represent the primary defense against microbial threats playing a pivotal role in maintaining tissue homeostasis. This review examines the multifaceted involvement of neutrophils in periodontitis, a chronic inflammatory condition affecting the supporting structures of teeth summarizing the contribution of neutrophil dysfunction in periodontitis and periodontal-related comorbidities. Periodontitis, a pathological condition promoted by dysbiosis of the oral microbiota, is characterized by the chronic inflammation of the gingiva and subsequent tissue destruction. Neutrophils are among the first immune cells recruited to the site of infection, releasing antimicrobial peptides, enzymes, and reactive oxygen species to eliminate pathogens. The persistent inflammatory state in periodontitis can lead to aberrant neutrophil activation and a sustained release of proinflammatory mediators, finally resulting in tissue damage, bone resorption, and disease progression. Growing evidence now points to the correlation between periodontitis and systemic comorbidities. Indeed, the release of inflammatory mediators, immune complexes, and oxidative stress by neutrophils, bridge the gap between local and systemic immunity, thus highlighting neutrophils as key players in linking periodontal inflammation to chronic conditions, including cardiovascular diseases, diabetes mellitus, and rheumatoid arthritis. This review underscores the crucial role of neutrophils in the pathogenesis of periodontitis and the complex link between neutrophil dysfunction, local inflammation, and systemic comorbidities. A comprehensive understanding of neutrophil contribution to periodontitis development and their impact on periodontal comorbidities holds significant implications for the management of oral health. Furthermore, it highlights the need for the development of novel approaches aimed at limiting the persistent recruitment and activation of neutrophils, also reducing the impact of periodontal inflammation on broader health contexts, offering promising avenues for improved disease management and patient care. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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13 pages, 2429 KiB  
Review
Mycobacterium tuberculosis in a Trap: The Role of Neutrophil Extracellular Traps in Tuberculosis
by Luiz Henrique Agra Cavalcante-Silva, Fernanda Silva Almeida, Arthur Gomes de Andrade, Fernando Cézar Comberlang, Leonardo Lima Cardoso, Shayenne Eduarda Ramos Vanderley and Tatjana S. L. Keesen
Int. J. Mol. Sci. 2023, 24(14), 11385; https://doi.org/10.3390/ijms241411385 - 13 Jul 2023
Cited by 2 | Viewed by 2840
Abstract
Mycobacterium tuberculosis complex causes tuberculosis (TB), a disease that causes pulmonary inflammation but can also affect other tissues. Despite macrophages having a defined role in TB immunopathogenesis, other innate immune cells, such as neutrophils, are involved in this process. These cells have high [...] Read more.
Mycobacterium tuberculosis complex causes tuberculosis (TB), a disease that causes pulmonary inflammation but can also affect other tissues. Despite macrophages having a defined role in TB immunopathogenesis, other innate immune cells, such as neutrophils, are involved in this process. These cells have high phagocytic ability and a microbial-killing machine comprised of enzymes, antimicrobial peptides, and reactive oxygen species. In the last two decades, a new neutrophil immune response, the neutrophil extracellular traps (NETs), has been intensely researched. NETs comprise DNA associated with histones, enzymes, and antimicrobial peptides. These structures are related to antimicrobial immune response and some immuno-pathogenesis mechanisms. This mini review highlights the role of NETs in tuberculosis and how they can be helpful as a diagnostic tool and/or therapeutic target. Full article
(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases 2.0)
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