Neutrophils, Fast and Strong 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 10062

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Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia
Interests: neutrophils; leukotrienes; inflammation; apoptosis; oxidative stress
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Dear Colleagues,

The history of medicine is also the history of our understanding of the role of neutrophils in the protection of our body. Ilya I. Mechnikov discovered that phagocytes and phagocytosis are the basis of natural cellular immunity, and macrophages and microphages (later renamed neutrophils) are the first line of defense in the host’s response to damage, infection, and tissue repair. Further research only confirmed the unique role of neutrophils (polymorphonuclear leukocytes) as independent defenders and acting in interaction with other cells in protecting the host. A characteristic property of neutrophils is their ability to migrate and penetrate into tissues, including inflammation loci, tumors and the central nervous system. In all places, the unique ability of neutrophils to activate and secrete aggressive products results in the destruction of pathogenic microorganisms, which finally leads to the damping of inflammatory processes. A detailed understanding of the functions of neutrophils will certainly help in understanding the mechanisms of the body’s immune defense. The clinical significance of blood neutrophils, tumor-associated neutrophils, and COVID-19-associated neutrophils, as well as those associated with other pathologies, is well established. Neutrophil-associated circulating markers of NETs are associated with COVID-19 disease severity and clinical outcome, including thrombotic events and intravascular coagulation. Bioactive lipid mediator storms occurring in severe COVID-19 include eicosanoids produced by neutrophils. Neutrophils release their own chemoattractant leukotriene B4, and leukotriene B4-mediated amplification mechanism is crucial for neutrophil swarming/clustering at sites of infection. Neutrophils are fast and strong and protect the body in all pathologies. In this context, the study of the functions of neutrophils in health and disease is of great interest and importance.

Prof. Dr. Galina F. Sud’ina
Guest Editor

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Keywords

  • neutrophil
  • phagocytosis
  • chemotaxis
  • secretion
  • degranulation
  • reactive oxygen species (ROS)
  • leukotrienes
  • neutrophil extracellular traps (NETs)
  • infection
  • inflammation
  • neutrophil swarming

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Published Papers (7 papers)

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Research

18 pages, 5080 KiB  
Article
Tbp and Hprt1 Are Appropriate Reference Genes for Splenic Neutrophils Isolated from Healthy or Tumor-Bearing Mice
by Khetam Sounbuli, Ludmila A. Alekseeva, Aleksandra V. Sen’kova, Innokenty A. Savin, Marina A. Zenkova and Nadezhda L. Mironova
Biomedicines 2024, 12(11), 2571; https://doi.org/10.3390/biomedicines12112571 - 10 Nov 2024
Viewed by 437
Abstract
Background/Objectives: Neutrophils have recently gained significant attention due to their heterogeneity in tumor settings. The gene expression profiles of neutrophils from different tumor types are of great interest. Murine splenic neutrophils reflect the immune status of the organism and could [...] Read more.
Background/Objectives: Neutrophils have recently gained significant attention due to their heterogeneity in tumor settings. The gene expression profiles of neutrophils from different tumor types are of great interest. Murine splenic neutrophils reflect the immune status of the organism and could be a source of tumor-associated neutrophils in tumor-bearing mice. However, information about appropriate reference genes for RT-qPCR analysis of murine neutrophils in the literature is lacking. The aim of this study was to identify stably expressed reference genes in murine splenic neutrophils. Methods: Bone marrow- and spleen-derived neutrophils were isolated from healthy C57Bl/6 and CBA/LacSto mice. Spleen-derived neutrophils were isolated from mice with Lewis lung carcinoma (LLC) and drug-resistant lymphosarcoma (RLS40). RNA was isolated and used for RT-qPCR analysis of 10 selected reference genes. Analysis of reference gene stability was performed using four different algorithms (BestKeeper, NormFinder, geNorm, ΔCt method), and comprehensive ranking was constructed using RefFinder. Results: The Ct values for the reference genes were in the range of 16.73–30.83 with the highest expression levels observed for B2m and the lowest for Sdha. Differences in the stability ranking performed by different algorithms were observed; however, the overall ranking of the studied reference genes was as follows, from most to least stably expressed: Tbp, Hprt1, Ywhaz, B2m, Gapdh, Actb, Sdha, Eef2, Rack1, and Rpl13a. Using Tbp or Rpl13a for RT-qPCR data normalization significantly affected the interpretation of target gene expression. Conclusions: Tbp and Hprt1 are recommended reference genes for murine splenic neutrophils regardless of their activation status. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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12 pages, 1016 KiB  
Article
Oxysterols Suppress Release of DNA from Granulocytes into Extracellular Space After Stimulation with Phorbol Myristate Acetate
by Yuichi Watanabe, Takashi Obama, Tomohiko Makiyama and Hiroyuki Itabe
Biomedicines 2024, 12(11), 2535; https://doi.org/10.3390/biomedicines12112535 - 6 Nov 2024
Viewed by 405
Abstract
Background: Neutrophils eject their DNA strings and cellular proteins into the extracellular space upon treatment with various stimulants. In the present study, we examined the effects of four major oxidized cholesterol metabolites on DNA release from granulocytes. Methods and Results: When oxysterols were [...] Read more.
Background: Neutrophils eject their DNA strings and cellular proteins into the extracellular space upon treatment with various stimulants. In the present study, we examined the effects of four major oxidized cholesterol metabolites on DNA release from granulocytes. Methods and Results: When oxysterols were added to HL-60-derived granulocytes stimulated with phorbol 12-myristate 13-acetate (PMA), they suppressed the release of DNA and myeloperoxidase from the cells. Among the four oxysterols tested, 7-ketocholesterol was the most effective. Addition of the same concentration of 7-ketocholesterol did not induce any cytotoxic effects, as evaluated based on the release of lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assays. DNA release from human peripheral blood neutrophils after PMA stimulation was also suppressed by 7-ketocholesterol. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to quantify sterol content in the cells. The addition of oxysterols increased the cellular content of the corresponding compounds by more than 10-fold compared to those at baseline. Treatment of HL-60-derived granulocytes with methyl-β-cyclodextrin that removes sterol compounds from the membranes increased DNA release from the cells in a dose-dependent manner. Conclusions: These results suggest that oxysterols have suppressive effects on DNA release from granulocytes stimulated with PMA. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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13 pages, 2741 KiB  
Article
Endothelial Biomarkers Are Superior to Classic Inflammatory Biomarkers in Community-Acquired Pneumonia
by Paula González-Jiménez, Mónica Piqueras, Ana Latorre, Jordi Tortosa-Carreres, Noé Mengot, Ricardo Alonso, Soledad Reyes, Isabel Amara-Elori, Luis Martínez-Dolz, Antonio Moscardó, Rosario Menéndez and Raúl Méndez
Biomedicines 2024, 12(10), 2413; https://doi.org/10.3390/biomedicines12102413 - 21 Oct 2024
Viewed by 624
Abstract
Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to [...] Read more.
Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to classic inflammation markers (C Reactive Protein [CRP] and procalcitonin [PCT]) in patients admitted for CAP and their relationship with ICU admission, CVE and mortality in the short and long term; Methods: Biomarkers were analysed in 515 patients with CAP at day 1, 285 at day 5 and 280 at day 30. Traditional inflammatory biomarkers and endothelial damage biomarkers were measured. ICU admission, CVE and mortality (in-hospital and 1-year follow-up) were assessed using receiver operating characteristic (ROC) curve analysis and univariate logistic regression. Results: A statistically significant association was observed between initial, raised CT-proET-1 and MR-proADM levels, the need for ICU admission and the development of in-hospital CVE or in-hospital mortality. Both endothelial markers maintained a strong association at day 30 with 1-year follow-up CVE. At day 1, CRP and PCT were only associated with ICU admission. On day 30, there was no association between inflammatory markers and long-term CVE or death. The odds ratio (OR) and area under the curve (AUC) of endothelial biomarkers were superior to those of classic biomarkers for all outcomes considered. Conclusions: Endothelial biomarkers are better indicators than classic ones in predicting worse outcomes in both the short and long term, especially CVE. MR-proADM is the best biomarker for predicting complications in CAP. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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13 pages, 2531 KiB  
Article
New Neutrophil Parameters in Diseases with Various Inflammatory Processes
by Elżbieta Rutkowska, Iwona Kwiecień, Agata Raniszewska, Rafał Sokołowski, Joanna Bednarek, Karina Jahnz-Różyk, Andrzej Chciałowski and Piotr Rzepecki
Biomedicines 2024, 12(9), 2016; https://doi.org/10.3390/biomedicines12092016 - 4 Sep 2024
Viewed by 707
Abstract
The neutrophils evaluation seems interesting in the initial qualifications of patients with various inflammatory processes. In this study, we presented analysis of neutrophils and new parameters of the complexity (NEUT-GI, NE-WX), maturation (IG), size (NE-FSC, NE-WZ), and neutrophil activities (NEUT-RI, NE-WY) in coronavirus [...] Read more.
The neutrophils evaluation seems interesting in the initial qualifications of patients with various inflammatory processes. In this study, we presented analysis of neutrophils and new parameters of the complexity (NEUT-GI, NE-WX), maturation (IG), size (NE-FSC, NE-WZ), and neutrophil activities (NEUT-RI, NE-WY) in coronavirus disease 2019 (COVID-19), lung cancer (LC), sarcoidosis (SA), and healthy controls (HCs). Peripheral blood (PB) was collected. The new parameters were examined by the Sysmex XN-1500. The mean absolute value for the IG parameter was the highest in the LC group. The differences in NEUT-RI value between COVID-19 and the HC group were observed. No significant differences were noticed between groups in the NEUT-GI granularity parameter. Neutrophil size assessed by NE-FSC parameter was reduced in all groups compared to HCs. The values of complexity (NE-WX), fluorescence (NE-WY), and size (NE-WZ) were the lowest in the HCs, whereas the highest median proportions of NE-WX, NE-WY, and NE-WZ were in LC patients. Patients from the SA group differed significantly from the HC group only for the NE-WZ parameter. We showed the usefulness of neutrophil parameters and their reactivity, morphology, and exhaustion. A more detailed analysis of blood counts may reveal trends that indicate a disease-specific immune response. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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12 pages, 1037 KiB  
Article
Correlation between Neutrophil-to-Lymphocyte Ratio and Cerebral Edema in Children with Severe Diabetic Ketoacidosis
by Alexandra-Cristina Scutca, Delia-Maria Nicoară, Niculina Mang, Iulius Jugănaru, Giorgiana-Flavia Brad and Otilia Mărginean
Biomedicines 2023, 11(11), 2976; https://doi.org/10.3390/biomedicines11112976 - 5 Nov 2023
Cited by 3 | Viewed by 1791
Abstract
Diabetic ketoacidosis (DKA), a common onset modality of type 1 diabetes mellitus (T1DM), can lead, in rare instances, to the development of cerebral edema, which is the leading cause of mortality in T1DM. Aside from the identification of several demographic and clinical risk [...] Read more.
Diabetic ketoacidosis (DKA), a common onset modality of type 1 diabetes mellitus (T1DM), can lead, in rare instances, to the development of cerebral edema, which is the leading cause of mortality in T1DM. Aside from the identification of several demographic and clinical risk factors for cerebral edema, attention has also been drawn to the possible link between systemic inflammation and neuroinflammation. This single-center retrospective study of 98 children with severe DKA aimed to investigate the possible relationship between neutrophil-to-lymphocyte ratio NLR) levels and the presence of cerebral edema. Patients were classified into three groups: alert (n = 28), subclinical cerebral edema (n = 59), and overt cerebral edema (n = 11). Lower blood pH and elevated NLR and blood urea were correlated with the presence of cerebral edema (p < 0.001). After a multivariable risk adjustment for possible confounding factors, such as age, pH, corrected sodium, and BUN, the NLR remained positively associated with cerebral edema (p = 0.045). As such, NLR may be an additional instrument to help practitioners target patients with a higher risk of severe cerebral edema. These patients would benefit from more rigorous neurologic surveillance, enabling the prompt identification of early signs of cerebral edema. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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13 pages, 2551 KiB  
Article
ROS Production by a Single Neutrophil Cell and Neutrophil Population upon Bacterial Stimulation
by Svetlana N. Pleskova, Alexander S. Erofeev, Alexander N. Vaneev, Petr V. Gorelkin, Sergey Z. Bobyk, Vasilii S. Kolmogorov, Nikolay A. Bezrukov and Ekaterina V. Lazarenko
Biomedicines 2023, 11(5), 1361; https://doi.org/10.3390/biomedicines11051361 - 4 May 2023
Cited by 4 | Viewed by 2072
Abstract
The reactive oxygen species (ROS) production by a single neutrophil after stimulation with S. aureus and E. coli was estimated by an electrochemical amperometric method with a high time resolution. This showed significant variability in the response of a single neutrophil to bacterial [...] Read more.
The reactive oxygen species (ROS) production by a single neutrophil after stimulation with S. aureus and E. coli was estimated by an electrochemical amperometric method with a high time resolution. This showed significant variability in the response of a single neutrophil to bacterial stimulation, from a “silent cell” to a pronounced response manifested by a series of chronoamperometric spikes. The amount of ROS produced by a single neutrophil under the influence of S. aureus was 5.5-fold greater than that produced under the influence of E. coli. The response of a neutrophil granulocyte population to bacterial stimulation was analyzed using luminol-dependent biochemiluminescence (BCL). The stimulation of neutrophils with S. aureus, as compared to stimulation with E. coli, caused a total response in terms of ROS production that was seven-fold greater in terms of the integral value of the light sum and 13-fold greater in terms of the maximum peak value. The method of ROS detection at the level of a single cell indicated the functional heterogeneity of the neutrophil population, but the specificity of the cellular response to different pathogens was the same at the cellular and population levels. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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10 pages, 1288 KiB  
Article
High Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Are Associated with a Higher Risk of Hemodialysis Vascular Access Failure
by Edoardo Pasqui, Gianmarco de Donato, Elisa Lazzeri, Cecilia Molino, Giuseppe Galzerano, Michele Giubbolini and Giancarlo Palasciano
Biomedicines 2022, 10(9), 2218; https://doi.org/10.3390/biomedicines10092218 - 7 Sep 2022
Cited by 14 | Viewed by 2652
Abstract
Our aim was to determine the predictive role of the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in vascular access malfunctioning in patients who had undergone their first native arterio-venous fistula (AVF) for hemodialysis. Methods: This was a single-center retrospective observational study. [...] Read more.
Our aim was to determine the predictive role of the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in vascular access malfunctioning in patients who had undergone their first native arterio-venous fistula (AVF) for hemodialysis. Methods: This was a single-center retrospective observational study. All patients who underwent the procedure of the creation of a first native AVF for hemodialysis from January 2019 to December 2020 were considered eligible to be part of this study. Reinterventions for AVF malfunctioning were registered and the population was subdivided into two groups with respect to AVF malfunctioning. ROC curves were obtained to find the appropriate cut-off values for the NLR and PLR. A multivariate analysis was used to identify the independent predictors for an AVF malfunction. Kaplan–Meier curves were used to evaluate the AVF patency rates. A total of 178 patients were enrolled in the study, of them 70% (n = 121) were male. The mean age was 67.5 ± 12 years. Reinterventions for AVF malfunctioning were performed on 102 patients (57.3%). An NLR > 4.21 and a PLR > 208.8 was selected as the cut-off for AVF malfunctioning. The study population was divided into two groups depending on the NLR and PLR values of the individual. For the NLR < 4.21 group, the AVF patency rates were 90.7%, 85.3%, and 84% at the 3-, 6-, and 12-month follow-up, respectively, and 77.5%, 65.8%, and 39.3% at 3, 6, and 12 months for the NLR > 4.21 group, respectively (p < 0.0001). For the PLR < 208.8 group, the patency rates were 85.6%, 76.7%, and 67.7% at the 3-, 6-, and 12-month follow-up. For the PLR > 208.28 group, the patency rates were 80.8%, 71.2%, and 50.7% for the 3-, 6-, and 12-month follow-up, respectively (p = 0.014). The multivariate analysis highlighted that diabetes mellitus, the neutrophil count, the lymphocyte count, and the NLR were independent risk factors for an AVF failure. In our experience, the NLR and PLR are useful markers for the stratification of vascular access failure in hemodialysis patients. The inexpensive nature and ready availability of the values of these biomarkers are two points of strength for everyday clinical practice. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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