Role Of Neutrophil Granulocytes Research Articles

The role of neutrophilic granulocytes and cationic proteins as biomarkers of the severity of the course of infectious and non-infectious animal diseases animal diseases

Innate immunity plays a decisive role in the primary reaction of the body to microbial agents. It is realized through the activation of cellular and humoral factors of nonspecific resistance – neutrophils, macrophages and antimicrobial and regulatory substances secreted by them, which, in turn, trigger a cascade of reactions involving lymphocytes. On the surface of the mucous membranes and in mucosal secretions, neutrophils realize their function not only through phagocytosis, but also through the release of DNA and bactericidal granules that form neutrophil extracellular traps. Violation of the functioning of these cells on the surface of the mucous membranes is considered as one of the factors of the formation of pathological microbial communities, leading to the development of dysbiosis and inflammation of various localization. The completed character of phagocytosis is provided by microbicidal systems of leukocytes: cationic proteins and myeloperoxidase. They have a special immunological significance and influence the course and outcome of the disease. Myeloperoxidase and cationic proteins are the main factors of bactericidal protection.

The role of neutrophil extracellular traps (NETs) in the immunopathogenesis of severe COVID-19: potential immunotherapeutic strategies regulating NET formation and activity

The role of neutrophil granulocytes (NG) in the pathogenesis of COVID-19 is associated with the NG recruitment into inflammatory foci, activation of their functions and enhanced formation of neutrophil extracellular networks (NETs). In this review, we analyzed a large body of scientific literature devoted to the features of developing NETs, their role in the COVID-19 pathogenesis, a role in emerging immunothrombosis, vasculitis, acute respiratory distress syndrome, cytokine storm syndrome, and multi-organ lesions. Convincing data are presented clearly indicating about a profound role of NETs in the COVID-19 immunopathogenesis and associated severe complications resulting from intensified inflammation process, which is a key for the course of SARS-CoV-2 virus infection. The presented role of NGs and NETs, along with that of other immune system cells and pro-inflammatory cytokines, is extremely important in understanding development of overactive immune response in severe COVID-19. The scientific results obtained available now allow to identify an opportunity of regulatory effects on hyperactivated NGs, NETosis at various stages and on limiting a negative impact of pre-formed NETs on various tissues and organs. All the aforementioned data should help in creating new, specialized immunotherapy strategies designed to increase the odds of survival, reduce severity of clinical manifestations in COVID-19 patients as well as markedly reduce mortality rates. Currently, it is possible to use existing drugs, while a number of new drugs are being developed, the action of which can regulate NG quantity, positively affect NG functions and limit intensity of NETosis. Continuing research on the role of hyperactive NG and NETosis as well as understanding the mechanisms of regulating NET formation and restriction in severe COVID-19, apparently, are of high priority, because in the future the new data obtained could pave the basis for development of targeted approaches not only for immunotherapy aimed at limiting education and blocking negative effects already formed NETs in severe COVID-19, but also for immunotherapy, which could be used in combination treatment of other netopathies, primarily autoimmune diseases, auto-inflammatory syndromes, severe purulent-inflammatory processes, including bacterial sepsis and hematogenous osteomyelitis.

Morbidity and Mortality of Neutropenic Patients in Visceral Surgery: A Narrative Review

Leukocytes are essential for the function of the immune system and cell–cell interaction in the human body, but hematological diseases as well as chemotherapeutic treatments due to cancer lead to occasionally or even permanent leukocyte deficiency. Normally, more than 50% of leukocytes are neutrophilic granulocytes, and leukopenia is, therefore, mostly characterized by a decrease in neutrophilic granulocytes. The consequence of neutropenia is increased susceptibility to infection, but also healing disorders are suggestable due to the disturbed cell–cell interaction. While there is no surgical treatment for leucocyte disorders, patients suffering from neutropenia are sometimes in need of surgery for other reasons. Less is known about the morbidity and mortality of this patients, which is why this narrative review critically summarizes the results of recent research in this particular field. The results of this review suggest that neutropenic patients in need of emergency surgery have a higher mortality risk compared to non-neutropenic patients. In contrast, in elective surgery, there was not a clear tendency for a higher mortality risk of neutropenic patients. The role of neutrophilic granulocytes in inflammation and immunity in surgical patients is emphasized by the results, but most of the evaluated studies showed methodological flaws due to small sample sizes or risk of bias. Further research has to evaluate the risk for postoperative complications, particularly of infectious complications such as surgical site infections, in neutropenic patients undergoing elective surgery, and should address the role of neutrophilic function in postoperative morbidity and mortality.

The role of neutrophilic granulocytes in the development of acute lung injury in experimental diabetes mellitus

Diabetes mellitus takes one of the first places in the structure of endocrine diseases. Among the complications of diabetes are sufficiently described nephro- and retinopathy, neuropathy, damage to the cardiovascular system. However, changes in the respiratory system and, in particular, the state of the endothelium of the pulmonary hemocapillaries and the morphofunctional state of neutrophilic granulocytes remain poorly understood. The aim of this study was to determine the role of neutrophilic granulocytes in the pathogenesis of acute lung injury in experimental diabetes mellitus. The experiments were performed on 88 white male Wistar rats weighing 170-210 g. The animals were divided into three groups: 1 – intact (n=10); 2 – control (n=40); 3 – experimental (n=38) with a model of diabetes mellitus, which was reproduced by intraperitoneal administration of streptozotocin company “Sigma” (USA), diluted in 0.1 M citrate buffer with pH 4.5, at a rate of 60 mg/kg body weight. An equivalent dose of 0.1 M citrate buffer solution with a pH of 4.5 was intraperitoneally administered to the control group of animals. Pulmonary tissue collection for electron microscopic examination was performed under thiopental anesthesia 14, 28, 42, 70 days after streptozotocin administration. Pieces of lung tissue were fixed in 2.5 % glutaraldehyde solution, followed by fixation in 1 % osmium tetroxide solution. After dehydration, the material was poured into epon-araldite. Sections obtained on an ultramicrotome “Tesla BS-490” were studied in an electron microscope “PEM-125K”. It was found that in the early stages of diabetes mellitus (14-28 days) there is a violation of the rheological properties of blood, as evidenced by erythrocyte aggregates, excessive accumulation of neutrophils, their adhesion and aggregation in the hemocapillaries of the alveolar wall. With the extension of the experiment (42-70 days) there is a progressive violation of the ultrastructural organization of hemocapillaries of the alveolar wall and pronounced changes in the rheological properties of blood. Erythrocyte sludges and leuco-platelet aggregates are determined in the lumen of microvessels. Increased permeability of hemocapillaries of the alveolar wall leads to the emigration of neutrophilic granulocytes into the interstitium and the lumen of the alveoli with the development of interstitial and intraalveolar edema. Thus, streptozotocin-induced diabetes is accompanied by the development of acute lung damage in the pathogenesis of which the leading role belongs to neutrophilic granulocytes. The nature and severity of changes in the lungs depends on the duration of exposure to hyperglycemia.

The Role of Neutrophilic Granulocytes in Philadelphia Chromosome Negative Myeloproliferative Neoplasms.

Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are composed of polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The clinical picture is determined by constitutional symptoms and complications, including arterial and venous thromboembolic or hemorrhagic events. MPNs are characterized by mutations in JAK2, MPL, or CALR, with additional mutations leading to an expansion of myeloid cell lineages and, in PMF, to marrow fibrosis and cytopenias. Chronic inflammation impacting the initiation and expansion of disease in a major way has been described. Neutrophilic granulocytes play a major role in the pathogenesis of thromboembolic events via the secretion of inflammatory markers, as well as via interaction with thrombocytes and the endothelium. In this review, we discuss the molecular biology underlying myeloproliferative neoplasms and point out the central role of leukocytosis and, specifically, neutrophilic granulocytes in this group of disorders.

Pathways of Neutrophil Granulocyte Activation in Hereditary Angioedema with C1 Inhibitor Deficiency

Hereditary angioedema (HAE) with C1-inhibitor deficiency belongs to bradykinin-mediated angioedemas. It is characterized by recurrent subcutaneous and/or submucosal swelling episodes (HAE attacks) and erythema marginatum skin rash as a pre-attack (prodromal) phase. HAE attacks were shown to be accompanied by peripheral blood neutrophilia. We aimed to find molecular mechanisms that may explain the distinct role of neutrophil granulocytes in HAE. Plasma levels of blood cells and factors related to neutrophil activation (cytokines, chemokines, chemotactic factors, enzymes, and neutrophil extracellular trap) were measured in plasma samples obtained from patients during symptom-free periods (n = 77), during prodromal phase (n = 8) and attacks (n = 14), during a spontaneously resolved attack (n = 1), and in healthy controls (n = 79). Higher counts of white blood cells, lymphocytes, and neutrophil granulocytes were found in symptom-free patients compared with controls; these cell counts were elevated further during HAE attacks. The level of chemokine (C–C motif) ligand 5, monocyte chemoattractant protein-1, and myeloperoxidase were also higher in the symptom-free patients than in the controls. Levels of monocyte chemoattractant protein-1, leukotriene B4, neutrophil elastase, and myeloperoxidase were elevated during attacks. During erythema marginatum, white blood cells and monocyte count and levels of interleukin 8 were elevated compared with symptom-free period. Similar changes were detected during the attack follow-up. We conclude that the activation of NGs in symptom-free periods and a further increase observed during attacks suggests that NGs may be involved in the pathomechanism of HAE with C1-INH deficiency.

Formation of Neutrophil Extracellular Traps when Modeling Plague Infection in Mice Immunized with Yersinia pestis EV NIIEG

The purpose of the study was to determine the effect of Yersinia pestis EV NIIEG on the process of neutrophil extracellular traps formation in vivo when modeling plague infection and assess their contribution to antiplague protection.Materials and methods. BALB/c mice, which were immunized subcutaneously with the Y. pestis EV NIIEG vaccine strain, were used in the study. Animals were infected with a virulent strain Y. pestis 231 at a dose of 20 LD50 (103 CFU). To evaluate the contribution of neutrophil extracellular traps (NETs) to antibacterial protection, an experimental model was used based on fermenting NETs in the abdominal cavity of mice with nuclease. To calculate the number of NETs in peritoneal exudate (PE) fluorescent microscopy was applied. Phagocytic activity of PE cells was determined by flow cytometry. Bactericidal effect of NETs was recorded using bacteriological method.Results and discussion. In pre-immunized mice, the process of NETs formation in response to the reintroduction of plague microbe living cells was 5 times more intense than in intact animals and was accompanied by a significant increase in the killing of Y. pestis cells in PE. The use of micrococcus nuclease in the experiment for fermentation of the NETs, produced in the body of immunized animals, provided evidence of NET participation in conferring anti-infective protection against plague infection. Thus, the established fact of the NET formation in case of Y. pestis infection of mice immunized with Y. pestis EV NIIEG vaccine strain and the influence of this process on the effectiveness of protection against plague is the basis for further clarifying the immunopathogenetic role of neutrophil granulocytes in plague.

Роль нейтрофильных гранулоцитов в развитии эндометриоза

Роль нейтрофильных гранулоцитов в развитии эндометриоза

Иммунные нарушения при остром пиелонефрите. Часть I

In the part I of a literature review of modern national and foreign publications dedicated to the problem of immune disorders in acute pyelonephritis, information on the role of innate and adaptive immunity in the pathogenesis of acute pyelonephritis is summarized and systematized. The relationship between the pathogens and immune system, in particular the ability of pathogens to overcome the protective immune mechanisms are discussed. The role of neutrophilic granulocytes as well as cellular immunity in the pathogenesis of acute pyelonephritis is shown. The changes in level of pro- and anti-inflammatory cytokines are separately highlighted. In conclusion, perspective directions for the studies in the area of immune disorders in acute pyelonephritis are proposed.

THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS

Over last decade, the importance of immune mechanisms for development of psoriasis has expanded considerably. This review describes biological properties of the cytokines from the interleukin-36 (IL-36) family, and their role in pathogenesis of plaque psoriasis, generalized pustular psoriasis and psoriatic arthritis. Keratinocytes and dendritic cells (DC) are the main sources of IL-36 in the skin. Production of this cytokine is greatly enhanced by inflammation. The studies have shown that, in affected skin of psoriatic patients, an increased expression of IL-36α and IL-36γ is observed. IL-36γ can be considered a specific marker of psoriasis, which is not found in other inflammatory skin diseases (neurodermatitis, lichen planus, eczema). The levels of this cytokine correlate with severity of psoriasis and decreases after anti-TNFα therapy. High level of IL-36 cytokines in the areas of psoriatic eruptions correlates with increased concentrations of pro-inflammatory TNFα, IL-17, IL-22 and IFNγ in the skin. We present literature data on the role of IL-36RN mutation which encodes the IL-36ra receptor antagonist, playing a role in the development of generalized pustular psoriasis (GPP). Excessive activity of IL-36 agonists leading to accumulation of neutrophilic granulocytes in epidermis may be a key event in the GPP pathogenesis. The article deals with modern ideas about the role of neutrophilic granulocytes in development of chronic inflammatory processes underlying pathogenesis of psoriasis. Proteases of neutrophils (cathepsin G, elastase and proteinase-3) are potent IL-36 activating enzymes that increase activity of IL-36 cytokines up to 500 times. In this review, a new mechanism (netosis) is suggested for the role of neutrophils in immune response. During the netosis, a large number of cytokines, antimicrobial peptides, intracellular components, serine proteases are released into the extracellular space. Thus, they may be involved into initiation and maintenance of a chronic inflammatory process in psoriasis. The present information concerning a role of new IL-36 family cytokines as one of the main psoriasis mediators has opened new therapeutic goals for the treatment of this disease and development of new methods of targeted therapy. Specific blocking of IL-36R signaling, or inhibition of neutrophil proteases of cathepsin G, neutrophil elastase that activate members of the IL-36 family, is likely to be a successful strategy in the therapy of psoriasis.

Beware the intruder: Real time observation of infiltrated neutrophils and neutrophil-Microglia interaction during stroke in vivo.

Inflammation plays an important role in the pathogenesis of ischemic stroke including an acute and prolonged inflammatory process. The role of neutrophil granulocytes as first driver of the immune reaction from the blood site is under debate due to controversial findings. In bone marrow chimeric mice we were able to study the dynamics of tdTomato-expressing neutrophils and GFP-expressing microglia after photothrombosis using intravital two-photon microscopy. We demonstrate the infiltration of neutrophils into the brain parenchyma and confirm a long-lasting contact between neutrophils and microglia as well as an uptake of neutrophils by microglia clearing the brain from peripheral immune cells.

Leukophages in canine semen.

Spermiophages and leukophages were found in teratozoospermic canine semen. Spermiophagy was the role of neutrophilic granulocytes. Leukophages are believed to be oversize macrophages transformed by and released from a chronic inflammatory lesion in the pelvic urethra or the prostate. The term leukophages was adopted to indicate that the cells phagocytize leukocytes, specifically neutrophilic granulocytes. Direct observations on living cells revealed a surprising interaction between these two cell types. It is inferred that neither of the phagocytic cells are related to the disturbed spermiogenesis nor the teratozoospermia.

Role of neutrophilic granulocytes in the defense against microbial infection. Signal transmission and the release of pro-inflammatory mediators

Role of neutrophilic granulocytes in the defense against microbial infection. Signal transmission and the release of pro-inflammatory mediators

Effect of experimental neutropenia on initial gingivitis in dogs

The role of neutrophilic granulocytes in the loss of gingival collagen has been studied by inducing experimental neutropenia during initial gingivitis in beagle dogs. Neutropenia was induced for 4 d in three animals with normal gingiva by repeated injections of rabbit anti-neutrophil serum. During neutropenia microbial plaque was allowed to form on the teeth. Samples of junctional (crevicular) leukocytes and gingival fluid were taken on days 0 and 4. Block biopsies of buccal gingiva were obtained on day 4. Stained semi- and ultrathin sections were used for histometric and stereologic tissue analysis. Gingival fluid flow increased from day 0 to day 4 in all dogs while junctional leukocytes increased in one dog only. Subgingival plaque had formed in most biopsies, and in the junctional epithelium very few neutrophilic granulocytes were present. In the coronal connective tissue subjacent to the junctional epithelium lymphoid cells, structurally abnormal neutrophilic granulocytes and monocytes/macrophages were diffusely scattered. The gingival collagen appeared mainly displaced by the inflammatory cells rather than dissolved. The data suggest that neutrophilic granulocytes may contribute to the loss of gingival collagen during initial gingivitis in dogs. The neutrophils also seem to be of importance for the limitation of subgingival plaque growth along the tooth surface.