Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology* ; Humans ; Atherosclerosis/immunology* ; Neutrophils/physiology* ; Leukocyte Elastase/metabolism* ; Peroxidase/physiology* ; Matrix Metalloproteinases/physiology* ; Cathepsin G/metabolism* ; Cathelicidins ; HMGB1 Protein/physiology* ; Histones ; Animals ; Endothelium, Vascular

The increasing aging population and aging-associated diseases have become a global issue for decades. People over 65 show an increased prevalence and greater severity of periodontitis, which poses threats to overall health. Studies have demonstrated a significant association between aging and the dysfunction of neutrophils, critical cells in the early stages of periodontitis, and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion. Neutrophils differentiate and mature in the bone marrow before entering the circulation; during an infection, they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens. Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues. The impacts of aging on neutrophils' chemotaxis, anti-microbial function, cell activation, and lifespan result in impaired neutrophil functions and excessive neutrophil activation, which could influence periodontitis course. We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses. We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging. This review could help us better understand the pathogenesis of periodontitis, which could offer novel therapeutic targets for periodontitis.
Humans ; Neutrophils/immunology* ; Periodontitis/immunology* ; Aging/physiology*

Gastric cancer (GC) is one of the most common tumor in the world, and remains a major public health problem and one of the leading causes of death. Recently many researches have demonstrated that systemic inflammatory response is associated with prognosis and response to therapy in gastric cancer, and the peripheral blood count test can partly reflect the systemic inflammatory response. Based on the peripheral blood count test, there are a lot of research regarding the relation between the platelet count (PLT), neutrophil, lymphocyte, white blood cell (WBC), neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio (PLR) with their prognostic role in gastric cancer. A high PLT and preoperative lymphocytopenia are both associated with increased lymph node metastasis, stage (III(+IIII(), serosal invasion (T3+T4) risk and poorer overall survival. Besides above, platelet monitoring following surgery can be applied to predict the recurrence for patients with GC that suffer preoperative high PLT but have restored PLT levels following resection. Moreover systemic inflammatory factors based on blood parameters, such as PLR, NLR and so on, have relation with the poor prognosis of patients with GC. Among them, high NLR is a negative predictor of prognosis in GC patients. However PLR remains inconsistent, while most researches demonstrated high PLR may be useful prognostic factor rather than independent prognostic factor. There are still some limitations which include various cut-off values, little of clinician attention, the uncertain mechanism, etc. Here we review the research progress in the prognostic role of the blood count test in gastric cancer.
Blood Cell Count ; methods ; statistics & numerical data ; Blood Platelets ; physiology ; Humans ; Inflammation ; blood ; diagnosis ; immunology ; Leukocyte Count ; statistics & numerical data ; Lymphatic Metastasis ; diagnosis ; immunology ; Lymphocyte Count ; statistics & numerical data ; Lymphopenia ; blood ; physiopathology ; Neoplasm Invasiveness ; immunology ; Neoplasm Recurrence, Local ; blood ; diagnosis ; Neoplasm Staging ; statistics & numerical data ; Neutrophils ; immunology ; Platelet Count ; statistics & numerical data ; Prognosis ; Stomach Neoplasms ; blood ; diagnosis ; immunology ; mortality ; Treatment Outcome

Asthma is a phenotypically heterogeneous chronic disease of the airways. Studies have found that neutrophils are crucial to airway inflammation in acute asthma, persistent asthma, particularly in asthma of poor response to glucocorticoid treatment. The role of neutrophils in development of bronchial asthma is complex, as they can release a potent source of cytokines and inflammatory mediators participating in asthma. Differing from eosinophilic inflammatory asthma, neutrophilic inflammatory asthma is not depend on helper T (Th)2 cells, but may be related to Th1 and Th17 cells. This review highlights the role of neutrophils in the development of asthma, and the treatment of neutrophilic asthma with biological agents and novel small molecules.
Asthma ; physiopathology ; therapy ; Cytokines ; Humans ; Inflammation ; physiopathology ; therapy ; Neutrophils ; immunology ; physiology ; Th1 Cells ; Th17 Cells

Neutrophil adhesion and migration are critical in hepatic ischemia/reperfusion (I/R) injury. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury. Therefore, the aim of this study was to assess the role of CD44 in neutrophil infiltration and liver injury from hepatic I/R. In this study, using a partial hepatic ischemic model in vivo, we determined the potential role of CD44 in neutrophil infiltration and liver injury from I/R. Reperfusion caused significant hepatocellular injury as it was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil recruitment and CD44 expression into the ischemic livers. Administration of anti-CD44 antibody to mice reduced the infiltration of neutrophil into the ischemic tissue, associated with liver function preservation. These results support crucial roles of CD44 in neutrophil recruitment and infiltration leading to liver damage in hepatic I/R injury. Moreover, they provide the rationale for targeting to CD44 as a potential therapeutic approach in liver I/R injury.
Alanine Transaminase/blood ; Animals ; Antibodies/immunology/pharmacology ; Antigens, CD44/immunology/metabolism/*physiology ; Cytokines/metabolism ; Disease Models, Animal ; Liver/*metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neutrophils/immunology/physiology ; Reperfusion Injury/metabolism/pathology/*prevention & control

BACKGROUNDPrimary percutaneous coronary interventions (PCI) have been proposed as a novel superior management strategy in patients with ST elevation myocardial infarction (STEMI). This study tested the hypothesis that in the acute phase of myocardial infarction with ST-segment elevation, the neutrophil/lymphocyte (N/L) ratio is a predictor of long-term prognosis.

METHODSWe analyzed 551 consecutive STEMI patients treated with primary PCI at a single university center. Patients were stratified according to quartiles of the mean neutrophil/lymphocyte ratio.

RESULTSKaplan-Meier survival analysis showed a cumulative eight-year survival of 94.2% in the first quartile, 92.0% in the second quartile, 91.3% in the third quartile, and 75.4% in the fourth quartile (P < 0.001 by log rank). Relative to patients in the other three lower N/L ratio quartiles, patients in the highest quartile were more than four times more likely to die during hospitalization (P < 0.001) and during long-term follow-up (P < 0.001). By multivariate Cox regression analysis including baseline demographic, clinical, and angiographic covariables, the N/L ratio in the highest quartile remained an independent predictor of mortality (hazard ratio 2.38, 95% confidence interval (CI) 1.42 to 3.98; P = 0.001).

CONCLUSIONThe neutrophil/lymphocyte ratio is a strong independent predictor of long-term mortality after ST elevation myocardial infarction treated with very early revascularization.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; CD4 Lymphocyte Count ; Electrocardiography ; Female ; Humans ; Lymphocytes ; physiology ; Male ; Middle Aged ; Myocardial Infarction ; immunology ; mortality ; therapy ; Neutrophils ; physiology ; Prognosis ; Proportional Hazards Models

Neutrophils play an important role in the human immune system for protection against such microorganisms as a protozoan parasite, Trichomonas vaginalis; however, the precise role of neutrophils in the pathogenesis of trichomoniasis is still unknown. Moreover, it is thought that trichomonal lysates and excretory-secretory products (ESP), as well as live T. vaginalis, could possibly interact with neutrophils in local tissues, including areas of inflammation induced by T. vaginalis in humans. The aim of this study was to investigate the influence of T. vaginalis lysate on the fate of neutrophils. We found that T. vaginalis lysate inhibits apoptosis of human neutrophils as revealed by Giemsa stain. Less altered mitochondrial membrane potential (MMP) and surface CD16 receptor expression also supported the idea that neutrophil apoptosis is delayed after T. vaginalis lysate stimulation. In contrast, ESP stimulated-neutrophils were similar in apoptotic features of untreated neutrophils. Maintained caspase-3 and myeloid cell leukemia-1 (Mcl-1) in neutrophils co-cultured with trichomonad lysate suggest that an intrinsic mitochondrial pathway of apoptosis was involved in T. vaginalis lysate-induced delayed neutrophil apoptosis; this phenomenon may contribute to local inflammation in trichomoniasis.
Animals ; *Apoptosis ; Cells, Cultured ; Female ; Humans ; Membrane Potentials ; Mitochondrial Membranes/physiology ; Neutrophils/chemistry/*immunology ; Receptors, IgG/analysis ; Trichomonas vaginalis/*immunology

In this study, we observed that lysophosphatidylglycerol (LPG) completely inhibited a formyl peptide receptor like-1 (FPRL1) agonist (MMK-1)-stimulated chemotactic migration in human phagocytes, such as neutrophils and monocytes. LPG also dramatically inhibited IL-1beta production by another FPRL1 agonist serum amyloid A (SAA) in human phagocytes. However, LPG itself induced intracellular calcium increase and superoxide anion production in human phagocytes. Keeping in mind that phagocytes migration and IL-1beta production by FPRL1 are important for the induction of inflammatory response, our data suggest that LPG can be regarded as a useful material for the modulation of inflammatory response induced by FPRL1 activation.
Chemotaxis, Leukocyte/*drug effects ; Humans ; Interleukin-1beta/*biosynthesis ; Lysophospholipids/*pharmacology ; Monocytes/drug effects/immunology/metabolism/physiology ; Neutrophils/drug effects/immunology/metabolism/physiology ; Peptides/metabolism/pharmacology ; *Phagocytes/drug effects/immunology/metabolism/physiology ; Receptors, Formyl Peptide/*metabolism ; Receptors, Lipoxin/*metabolism ; Serum Amyloid A Protein/metabolism/pharmacology

Dominant inflammatory cytokines might be different depending on the underlying causes of acute lung injury (ALI). The role of kertinocyte-derived chemokine (KC), a potent chemoattractant for neutrophils, has not been clearly established in hemorrhage-induced ALI. In this study, lung injury and cytokine expressison were evaluated in LPS- or hemorrhage-induced ALI models of BALB/c mice. The myeloperoxidase activities at 4 hr after hemorrhage and LPS-injection were 47.4+/-13.0 and 56.5+/-16.4 U/g, respectively. NF-kappa B activity peaked at 4 hr after hemorrhage, which was suppressed to the control level by anti-high mobility group B1 (HMGB1) antibody. Lung expressions of TNF-alpha, MIP-2, and IL-1beta were increased by LPS injection. However, there was only a minimal increase in IL-1beta and no expressions of TNF-alpha or MIP-2 in hemorrhage-induced ALI. In contrast, lung KC increased significantly at 4 hr after hemorrhage compared to control levels (83.1+/-12.3 vs. 14.2+/-1.6 pg/mL/mg by ELISA) (P<0.05). By immunohistochemical staining, lung neutrophils stained positive for KC. Increased KC was also observed in bronchoalveolar lavage fluid and plasma. KC plays an important role in hemorrhage-induced ALI.
Acute Lung Injury/etiology/*metabolism ; Animals ; Antibodies/immunology/metabolism ; Chemokine CXCL2/analysis ; Chemokines/analysis/blood/*physiology ; Chickens ; HMGB1 Protein/metabolism ; Humans ; Interleukin-1beta/analysis ; Lipopolysaccharides/toxicity ; Mice ; Mice, Inbred BALB C ; NF-kappa B/metabolism ; Neutrophils/immunology/metabolism ; Peroxidase/analysis ; Shock, Hemorrhagic/*complications ; Time Factors ; Tumor Necrosis Factor-alpha/analysis

Neutrophils are also known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. In this study, neutrophils were cultivated in vitro in the presence or absence of compounds modulating their survival in an attempt to characterize the expression profile of the DC markers. Higher MHC-II, CD80, CD86, CD83, and CD40 expression levels were detected on the surface of the cultured neutrophils for 24 h than on the freshly isolated cells. The annexin V-positive cells showed a higher expression level of the DC markers than the annexin V-negative cells. The population of neutrophils double stained with annexin V and the DC markers increased after being incubated with agonistic anti-Fas Ab. LPS, the anti-apoptotic compound, decreased the CD86 and MHC-II expression levels but 50-60% of the DC marker-positive cells were detected in the annexin V-positive cells. In contrast, CD80, CD86, CD83, and HLA-DR mRNA levels increased in the GM-CSF-treated neutrophils but not in the anti-Fas Ab-treated neutrophils. T cell proliferation was inhibited by co-culturing them with anti-Fas Ab- or LPS-treated neutrophils at a high neutrophil:T cell ratio. However, the superantigen-mediated T cell proliferation was increased by the LPS-treated neutrophils but decreased by the anti-Fas Ab-treated neutrophils. There was a lower level of interferon-gamma production in the T cells co-cultured with anti-Fas Ab-treated neutrophils than with the LPS-treated neutrophils. This suggests that apoptotic neutrophils express DC markers on their surface and the differential expression of DC markers might have a detrimental effect on the immune reaction.
Antigen Presentation ; Antigens, CD/biosynthesis ; Antigens, CD95/pharmacology ; Antigens, Differentiation/*biosynthesis ; *Apoptosis ; Cells, Cultured ; Dendritic Cells/*metabolism ; Humans ; Lipopolysaccharides/pharmacology ; Lymphocyte Activation ; Neutrophils/*metabolism/physiology ; T-Lymphocytes/immunology