Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that ...neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
Introduction:
Recently, neutrophil-to-lymphocyte ratio (NLR) has been proven to be useful in predicting severity, mortality, and morbidity of stroke. NLR is low cost and yet not used widely as a ...biomarker to predict prognosis.
Aims:
We evaluated the association of NLR in severity of stroke and ischemic stroke subtypes.
Methodology:
A total of 69 subjects with ischemic stroke onset within 24 h were included in the study and categorized according to TOAST classification. National Institutes of Health Stroke Scale was used to determine stroke severity at admission. Samples were obtained within 24 h of stroke onset and NLR measured which was later correlated with severity and subtypes of stroke.
Results:
NLR and severity of stroke showed statistically significant association (P < .05). Median (interquartile range IQR) of NLR was significantly high in severe cases (7.1 4.03-7.698), as compared to others. The area under the receiver operating characteristic curve for NLR to predict the stroke severity was 6.07 area under the curve 0.764; 95% confidence interval: 0.647 to 0.858). When NLR was more than 6.07, there was 90.90% chances of moderate-to-severe stroke and with milder stroke, 93.10% had NLR of less than equal to 6.07. NLR and stroke subtypes also showed statistically significant association (P < .05). Median (IQR) of NLR in embolic stroke was significantly high (4.75 2.95-8.2), as compared to other stroke subtypes.
Conclusion:
NLR, at a cut-off 6, has moderate sensitivity and higher specificity in predicting stroke severity and NLR was high in embolic stroke among other stroke subtypes.
Highlights • Neutrophil-lymphocyte-ratio and frequency of tumor-associated neutrophils are powerful and clinically relevant prognostic biomarkers in human oncology. • Peripheral blood low-density ...neutrophils are expanded in cancer patients and contain myeloid-derived suppressor cells. • Translation of mechanisms observed in murine models (including N1/N2 switch) to human oncology represents a current bottle neck in the field. • Identification and functional characterization of tumor-associated neutrophils and putative myeloid-derived suppressor cells in human tissues is another bottle neck in the field.
Neutrophils have always been considered as a short-lived and homogeneous cell type in the innate immune system, which have limited pro-inflammatory or anti-inflammatory effects. However, in recent 10 ...years, the understanding of neutrophils has been undergoing some kind of revival as researches progressed. The researches on the heterogeneity of neutrophils and the mechanism of their interaction with other immune cells have promoted the researchers to re-understand the physiological and pathophysiological roles of neutrophils. In the following decades, with the development of single-cell sequencing technology, spatial transcriptome sequencing technology, and multi-omics combined sequencing technology, researchers will have a better understanding of the biological behaviors of neutrophils. This paper briefly reviews the biological behaviors of neutrophils and their roles in various diseases in recent years.
Summary
Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated ...vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti‐lysosomal membrane protein‐2 (LAMP‐2) antibody, may have a pathogenic role in AAV. We have shown previously that anti‐LAMP‐2 antibody‐stimulated NET formation contains autoantigens and anti‐microbial peptides. The current study sought to determine whether LAMP‐2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti‐LAMP‐2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti‐LAMP‐2 antibody‐induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP‐2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti‐LAMP‐2 antibody, and this effect was attenuated by the inhibitors of autophagy 3‐methyladenine (3MA) and 2‐morpholin‐4‐yl‐8‐phenylchromen‐4‐one (LY294002). The anti‐LAMP‐2 antibody‐stimulated NET formation was unaffected by benzyloxycarbonyl‐Val‐ Ala‐Asp (OMe)‐fluoromethylketone (zVAD‐fmk) and necrostatin‐1 (Nec‐1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P = 0·0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti‐LAMP‐2 antibody. Our results provide further evidence that autophagy is involved in ANCA‐induced NET formation in human neutrophils.
Neutrophil migration and its role during inflammation has been the focus of increased interest in the past decade. Advances in live imaging and the use of new model systems have helped to uncover the ...behaviour of neutrophils in injured and infected tissues. Although neutrophils were considered to be short-lived effector cells that undergo apoptosis in damaged tissues, recent evidence suggests that neutrophil behaviour is more complex and, in some settings, neutrophils might leave sites of tissue injury and migrate back into the vasculature. The role of reverse migration and its contribution to resolution of inflammation remains unclear. In this Review, we discuss the different cues within tissues that mediate neutrophil forward and reverse migration in response to injury or infection and the implications of these mechanisms to human disease.
Neutrophil Extracellular Traps (NETs) are net-like structures composed of DNA-histone complexes and proteins released by activated neutrophils. In addition to their key role in the neutrophil innate ...immune response, NETs are also involved in autoimmune diseases, like systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and in other non-infectious pathological processes, as coagulation disorders, thrombosis, diabetes, atherosclerosis, vasculitis, and cancer. Recently, a large body of evidence indicates that NETs are involved in cancer progression and metastatic dissemination, both in animal models and cancer patients. Interestingly, a close correlation between cancer cell recruitment of neutrophils in the tumor microenvironment (Tumor Associated Neutrophils. TANs) and NET formation has been also observed either in primary tumors and metastatic sites. Moreover, NETs can also catch circulating cancer cells and promote metastasis. Furthermore, it has been reported that wake dormant cancer cells, causing tumor relapse and metastasis. This review will primarily focus on the pro-tumorigenic activity of NETs in tumors highlighting their ability to serve as a potential target for cancer therapy.
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