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Molecular Cancer Aug 2017Expression of high levels of immune cells including neutrophils has been associated with detrimental outcome in several solid tumors and new strategies to decrease their... (Review)
Review
Expression of high levels of immune cells including neutrophils has been associated with detrimental outcome in several solid tumors and new strategies to decrease their presence and activity are currently under clinical development. Here, we review some of the relevant literature of the role of neutrophils in different stages of the oncogenic process including tumor initiation, growth, proliferation or metastatic spreading and also focus on how neutrophil counts or the neutrophil-to-lymphocyte ratio may be used as a prognostic and predictive biomarker. Strategies to avoid the deleterious effects of neutrophils in cancer and to reduce their activity are discussed. Examples for such strategies include inhibition of CXCR1 and CXCR2 to decrease migration of neutrophils to tumoral areas or the inhibition of granulocyte colony stimulating factor to decrease the amount of neutrophils which has shown efficacy in preclinical models.
Topics: Humans; Leukocyte Count; Lymphocytes; Neoplasms; Neutrophils; Prognosis
PubMed: 28810877
DOI: 10.1186/s12943-017-0707-7 -
Cytometry. Part B, Clinical Cytometry Jan 2023Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic... (Review)
Review
Multiparameter flow cytometry in the evaluation of myelodysplasia: Analytical issues: Recommendations from the European LeukemiaNet/International Myelodysplastic Syndrome Flow Cytometry Working Group.
Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic syndrome (MDS). MFC can also be applied in the follow-up of MDS patients undergoing treatment. This document summarizes recommendations from the International/European Leukemia Net Working Group for Flow Cytometry in Myelodysplastic Syndromes (ELN iMDS Flow) on the analytical issues in MFC for the diagnostic work-up of MDS. Recommendations for the analysis of several BM cell subsets such as myeloid precursors, maturing granulocytic and monocytic components and erythropoiesis are given. A core set of 17 markers identified as independently related to a cytomorphologic diagnosis of myelodysplasia is suggested as mandatory for MFC evaluation of BM in a patient with cytopenia. A myeloid precursor cell (CD34 CD19 ) count >3% should be considered immunophenotypically indicative of myelodysplasia. However, MFC results should always be evaluated as part of an integrated hematopathology work-up. Looking forward, several machine-learning-based analytical tools of interest should be applied in parallel to conventional analytical methods to investigate their usefulness in integrated diagnostics, risk stratification, and potentially even in the evaluation of response to therapy, based on MFC data. In addition, compiling large uniform datasets is desirable, as most of the machine-learning-based methods tend to perform better with larger numbers of investigated samples, especially in such a heterogeneous disease as MDS.
Topics: Humans; Flow Cytometry; Myelodysplastic Syndromes; Antigens, CD34; Granulocytes; Monocytes; Immunophenotyping
PubMed: 36537621
DOI: 10.1002/cyto.b.22108 -
European Review For Medical and... Jun 2022Mesenteric ischemia is a fatal condition leading to ischemia and necrosis of the intestines following the interruption of blood flow in the vessels feeding the...
OBJECTIVE
Mesenteric ischemia is a fatal condition leading to ischemia and necrosis of the intestines following the interruption of blood flow in the vessels feeding the intestines. The present study investigated the significance of immature granulocyte count and delta neutrophil index in the early prediction of mesenteric ischemia.
PATIENTS AND METHODS
The study included 248 patients who applied to the hospital between 01.01.2020 and 01.04.2022 and underwent emergency and elective bowel resection in the general surgery clinic. The study population was divided into two groups as patients who underwent surgery for causes non-related to mesenteric ischemia (Group 1) and patients with findings of mesenteric ischemia who underwent laparotomy (Group 2). Preoperative immature granulocyte counts, and delta neutrophil index levels were compared between the groups with and without perioperative mesenteric ischemia.
RESULTS
No statistical difference was observed between the groups in terms of age or sex. Comparing the two groups regarding immature granulocyte count and delta neutrophil index revealed a statistically significant difference (p<0.001). The median immature granulocyte count was 0.04 (0.02-0.06) in Group 1 and 1.83 (0.18-2.5) in Group 2, with a statistically significant difference (p<0.001). Also, the comparison of delta neutrophil index levels revealed a median value of 0.4 (0.2-0.6) in Group 1 and 5.6 (0.7-8.1) in Group 2, with a statistically significant difference.
CONCLUSIONS
The results of this study have demonstrated that immature granulocyte counts, and delta neutrophil index levels are reliable markers that do not require any additional time or expense, can be easily measured in a complete blood count, and can be used for evaluating intestinal necrosis in mesenteric ischemia.
Topics: Biomarkers; Humans; Leukocyte Count; Mesenteric Ischemia; Necrosis; Neutrophils
PubMed: 35776022
DOI: 10.26355/eurrev_202206_29060 -
The Turkish Journal of Gastroenterology... Oct 2022This study aimed to investigate the utility of immature granulocyte count and percentage on the prediction of suspected acute appendicitis according to the Alvarado...
The Utility of Immature Granulocyte Count and Percentage on the Prediction of Acute Appendicitis in the Suspected Acute Appendicitis According to the Alvarado Scoring System: A Retrospective Cohort Study.
BACKGROUND
This study aimed to investigate the utility of immature granulocyte count and percentage on the prediction of suspected acute appendicitis according to the Alvarado scoring system and its effect on the need for computed tomography scanning.
METHODS
Adult patients who had an Alvarado scoring system between 4 and 7 with the first imaging technique computed tomography were included and retrospectively analyzed. The immature granulocyte count and granulocyte percentage were obtained from the blood samples taken at the time of the patient's first admission to the hospital.
RESULTS
A total of 652 patients were evaluated and 186 patients were included in the study. Acute appendicitis was not detected in computed tomography imaging of 121 (65%) patients (group N) and detected in 65 (35%) patients (group P). The mean immature granulocyte percentage in group N and group P were 0.314 ± 0.188 (0.00-1.40) and 0.364 ± 0.205 (0.05-1.00), respectively. The mean immature granulocyte percentage was similar between groups (P = .095). The mean immature granulocyte count was 33 ± 46/μL (0-50) in group N and 60 ± 85/μL (10-690) in group P. Immature granulocyte count was significantly higher in group P (P = .005). Univariate analysis results revealed that age and immature granulocyte percentage were not predictive factors for the presence of acute appen- dicitis in suspected cases (P > .05). On the other hand white blood cell, neutrophil-lymphocyte ratio, C-reactive protein, and immature granulocyte count were determined as predictive factors in univariate analysis and multivariate analysis. Receiver operating character- istic curve analysis of preoperative immature granulocyte percentage and immature granulocyte count values in the diagnosis of acute appendicitis: the cut-off value of immature granulocyte percentage was ≥0.35 and its sensitivity, specificity, positive predictive value, and negative predictive value were 44.1%, 72.1%, 71.1%, and 41.5%, respectively (area under the curve: 0.588; CI: 0.484-0.682). The cut-off value of immature granulocyte count was ≥35/μL and its sensitivity, specificity, positive predictive value, and negative predictive value were 66.1%, 73.6%, 71.9%, and 67.7%, respectively (area under the curve: 0.743; CI: 0.659-0.827) Conclusion: Immature granulocyte count is a predictive factor for acute appendicitis in patients with the middle-risk group according to the Alvarado score and may be useful for the selective use of tomography.
Topics: Acute Disease; Adult; Appendicitis; C-Reactive Protein; Granulocytes; Humans; Retrospective Studies; Sensitivity and Specificity
PubMed: 35946881
DOI: 10.5152/tjg.2022.21865 -
Acta Neurobiologiae Experimentalis 2023APOE‑ε4 genotype (apolipoprotein E, epsilon 4) is the strongest genetic risk factor for Alzheimer's disease (AD). Despite years of research, it is still not known how...
APOE‑ε4 genotype (apolipoprotein E, epsilon 4) is the strongest genetic risk factor for Alzheimer's disease (AD). Despite years of research, it is still not known how it contributes to dementia development. APOE has been implicated in many AD pathology mechanisms, like Aβ clearance, brain metabolism, changes within microglia and other glial functions and inflammatory processes. In fact, immunological/inflammatory processes are recently discussed as an important factor in Alzheimer's development and granulocyte profiles changes are reported in patients. However, the exact link between the immune system and risk‑genes is unknown. In particular, it is not known whether and how they interact throughout the lifetime, before the disease onset. The aim of the study was to investigate the relationship between granulocyte count and the APOE/PICALM genes in healthy individuals with an increased genetic risk of AD. An exploratory analysis regarding other blood cells was also conducted. Blood samples were collected from 77 healthy middle‑aged (50-63 years old) participants, who were also asked to complete a health and life‑style questionnaires. Groups with different AD risk‑genes were compared. Differences in granulocyte profiles were found in healthy carriers of AD risk‑genes who had slightly elevated eosinophil levels as compared to non-risk carriers. An exploratory analysis showed some alteration in mean corpuscular hemoglobin content and concentration (MCH/MCHC) levels between risk‑carriers subgroups and non-risk carriers. No other differences in blood count or lipoprotein profile were found between healthy APOE/PICALM risk‑carriers and non-risk carriers. Longitudinal studies will reveal if and how those changes contribute to the development of AD pathology.
Topics: Middle Aged; Humans; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Genotype; Erythrocytes; Granulocytes; Monomeric Clathrin Assembly Proteins
PubMed: 37493530
DOI: 10.55782/ane-2023-012 -
British Medical Bulletin Sep 2018Radionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of... (Review)
Review
INTRODUCTION
Radionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of leucocyte kinetics, to the next goal of positron emission tomography (PET).
SOURCES OF DATA
Mostly the authors' own studies, following on from studies of the early pioneers.
AREAS OF CONTROVERSY
From early imaging studies, it appeared that the majority of the marginated granulocyte pool was located in the lungs. However, later work disputed this by demonstrating the exquisite sensitivity of granulocytes to ex vivo isolation and labelling, and that excessive lung activity is artefactual.
AREAS OF AGREEMENT
Following refinement of labelling techniques, it was shown that the majority of marginated granulocytes are located in the spleen and bone marrow. The majority of leucocytes have a pulmonary vascular transit time only a few seconds longer than erythrocytes. The minority showing slow transit, ~5% in healthy persons, is increased in systemic inflammatory disorders that cause neutrophil priming and loss of deformability. Using a range of imaging techniques, including gamma camera imaging, whole-body counting and single photon-emission computerized tomography, labelled granulocytes were subsequently used to image pulmonary trafficking in lobar pneumonia, bronchiectasis, chronic obstructive pulmonary disease and adult respiratory distress syndrome.
GROWING POINTS
More recently, eosinophils have been separated in pure form using magnetic bead technology for the study of eosinophil trafficking in asthma.
AREAS TIMELY FOR DEVELOPING RESEARCH
These include advancement of eosinophil imaging, development of monocyte labelling, development of cell labelling with PET tracers and the tracking of lymphocytes.
Topics: Granulocytes; Humans; Isotope Labeling; Leukocytes; Lung Diseases; Positron-Emission Tomography; Radioisotopes
PubMed: 30052802
DOI: 10.1093/bmb/ldy022 -
Annals of Medicine 2023Predicting acute exacerbations (AEs) in chronic obstructive pulmonary disease (COPD) is crucial. This study aimed to identify blood biomarkers for predicting COPD...
INTRODUCTION
Predicting acute exacerbations (AEs) in chronic obstructive pulmonary disease (COPD) is crucial. This study aimed to identify blood biomarkers for predicting COPD exacerbations by inflammatory phenotypes.
MATERIALS AND METHODS
We analyzed blood cell counts and clinical outcomes in 340 COPD patients aged 20-90 years. Patients were categorized into eosinophilic inflammation (EOCOPD) and non-eosinophilic inflammation (N-EOCOPD) groups. Blood cell counts, eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) were calculated. Linear and logistic regression models assessed relationships between health outcomes and blood cell counts.
RESULTS
EOCOPD patients had distinct characteristics compared to N-EOCOPD patients. Increased neutrophil % and decreased lymphocyte % were associated with reduced pulmonary function, worse quality of life and more exacerbations, but they did not show statistical significance after adjusting by age, sex, BMI, smoking status, FEV1% and patient's medication. Subgroup analysis revealed a 1.372-fold increase in the OR of AE for every 1 unit increase in NLR in EOCOPD patients ( < .05). In N-EOCOPD patients, every 1% increase in blood eosinophil decreased the risk of exacerbation by 59.6%.
CONCLUSIONS
Our study indicates that distinct white blood cell profiles in COPD patients, with or without eosinophilic inflammation, can help assess the risk of AE in clinical settings.
Topics: Humans; Neutrophils; Eosinophils; Quality of Life; Disease Progression; Retrospective Studies; Leukocyte Count; Pulmonary Disease, Chronic Obstructive; Eosinophilia; Inflammation
PubMed: 38065676
DOI: 10.1080/07853890.2023.2285924 -
Molecular Medicine Reports Jul 2022Immature granulocytes (IGs) include metamyelocytes, myelocytes and promyelocytes, and are the precursors of neutrophils. Increased IG counts found in peripheral blood...
Immature granulocytes (IGs) include metamyelocytes, myelocytes and promyelocytes, and are the precursors of neutrophils. Increased IG counts found in peripheral blood indicate an enhanced bone marrow activity. In addition, IGs have been evaluated in numerous clinical conditions, such as severe acute pancreatitis, systemic inflammatory response syndrome and infectious complications following open‑heart surgery under cardiopulmonary bypass. Neutrophils are considered to play a crucial role in the host defense during bacterial and fungal infections, and are involved in the antiviral immune response. Numerous studies have reported the role of neutrophils in coronavirus disease 2019 (COVID‑19) infection, concluding that the percentage of neutrophils may be a predictor of the severity of COVID‑19 infection. There has been limited research regarding the role of neutrophil precursors in viral infections, including severe acute respiratory syndrome coronavirus 2 infection. The present thus aimed to evaluate the role of the IG count in patients hospitalized due to COVID‑19 infection. The patients were predominantly infected with the alpha variant and were all unvaccinated. The IG count was measured and was found to be associated with disease severity, with patient outcomes, with the duration of hospitalization and with the development of complications. The IG count was a significantly associated with the severity of COVID‑19 infection, with greater IG count values being detected in severe and critical cases. In addition, greater IG count values were associated with a longer duration of hospitalization. Furthermore, the IG count was found to be an independent prognostic biomarker of intubation and mortality in patients with COVID‑19, according to multivariate logistic regression analysis, including age, the male sex and the presence of comorbidities as confounders.
Topics: Acute Disease; Biomarkers; COVID-19; Granulocytes; Humans; Leukocyte Count; Male; Pancreatitis; SARS-CoV-2
PubMed: 35551416
DOI: 10.3892/mmr.2022.12733 -
Frontiers in Immunology 2022Neutrophil extracellular traps (NETs)-as double-edged swords of innate immunity-are involved in numerous processes such as infection, inflammation and tissue repair....
BACKGROUND
Neutrophil extracellular traps (NETs)-as double-edged swords of innate immunity-are involved in numerous processes such as infection, inflammation and tissue repair. Research on neutrophil granulocytes is limited because of their short lifetime of only a few hours. Several attempts have been made to prolong the half-life of neutrophils using cytokines and bacterial products and have shown promising results. These long-term surviving neutrophils are reported to maintain phagocytic activity and cytokine release; however, little is known regarding their capability to release NETs.
METHODS
We analysed the prolongation of neutrophil survival under various culture conditions using granulocyte colony-stimulating factor (G-CSF), lipopolysaccharide (LPS) or tumour necrosis factor alpha (TNF-α) by flow cytometry and a viability assay. Additionally, we assessed NET formation following stimulation with phorbol 12-myristate 13-acetate (PMA) by immunofluorescence staining, myeloperoxidase (MPO)-DNA sandwich-ELISA and fluorometric assays for cell-free DNA (cfDNA), neutrophil elastase (NE) and myeloperoxidase (MPO).
RESULTS
Untreated neutrophils could form NETs after stimulation with PMA for up to 24 h. Incubation with LPS extended their ability to form NETs for up to 48 h. At 48 h, NET release of neutrophils cultured with LPS was significantly higher compared to that of untreated cells; however, no significantly different enzymatic activity of NE and MPO was observed. Similarly, incubation with G-CSF resulted in significantly higher NET release at 48 h compared to untreated cells. Furthermore, NETs showed significantly higher enzymatic activity of NE and MPO after incubation with G-CSF. Lastly, incubation with TNF-α had no influence on NET release compared to untreated cells although survival counts were altered by TNF-α.
CONCLUSIONS
G-CSF, LPS or TNF-α each at low concentrations lead to prolonged survival of cultured neutrophils, resulting in considerable differences in NET formation and composition. These results provide new information for the use of neutrophils in long-term experiments for NET formation and provide novel insights for neutrophil behaviour under inflammatory conditions.
Topics: Cytokines; Granulocyte Colony-Stimulating Factor; Lipopolysaccharides; Neutrophils; Peroxidase; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha
PubMed: 35242132
DOI: 10.3389/fimmu.2022.815412 -
The Journal of Allergy and Clinical... Mar 2023Asthma is a disease that can be separated into different phenotypes and endotypes based on the clinical characteristics and the molecular mechanisms of the condition,...
BACKGROUND
Asthma is a disease that can be separated into different phenotypes and endotypes based on the clinical characteristics and the molecular mechanisms of the condition, respectively.
OBJECTIVE
To assess the association between blood eosinophil and neutrophil counts with clinical and molecular features in patients with adult-onset asthma.
METHODS
Blood eosinophil and neutrophil counts were measured from 203 patients who took part in the Seinäjoki Adult Asthma Study and attended the 12-year follow-up visit. The patients were then divided into four groups (paucigranulocytic [n = 108], neutrophilic [n = 60], eosinophilic [n = 21], and mixed granulocytic [n = 14]), according to eosinophil and neutrophil levels. The cutoff values used to define the groups were 0.30 × 10 · L for blood eosinophils and 4.4 × 10 · L for blood neutrophils.
RESULTS
The neutrophilic group had highest body mass index. It was dispensed the highest doses of inhaled corticosteroids during the 12-year follow-up and made the most unplanned respiratory visits. The neutrophilic, eosinophilic, and mixed granulocytic groups had more severe asthma compared with the paucigranulocytic group. The neutrophilic and eosinophilic groups were associated with higher dispensed antibiotics. The eosinophilic group had more nasal polyps, more suspected sinusitis, a greater decline in lung function, and increased levels of periostin, FeNO, and IgE. The neutrophilic group had increased high-sensitivity C-reactive protein, matrix metalloproteinase-9, IL-6, leptin, and soluble urokinase plasminogen activator receptor levels. The mixed granulocytic group showed increased resistin levels together with the neutrophilic group.
CONCLUSIONS
In addition to blood eosinophils, the blood neutrophil count reflects underlying inflammatory patterns and indicates important differences in asthma clinical features and outcomes.
Topics: Humans; Eosinophils; Neutrophils; Sputum; Asthma; Leukocyte Count
PubMed: 36473624
DOI: 10.1016/j.jaip.2022.11.025