4.7 Review

Neutrophils in chronic inflammatory diseases

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Innate Immune Cells in the Adipose Tissue in Health and Metabolic Disease

Zoi Michailidou et al.

Summary: This article discusses the role of innate immune cells in adipose tissue in obese states, and how these cells are influenced by the obesogenic microenvironment and humoral, paracrine, and cellular interactions. Additionally, it outlines the significant role of hypoxia in adipose tissue inflammation.

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Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients

Jingwen Du et al.

Summary: The levels of NETs markers were significantly higher in the plasma of NASH patients, and NETs derived from NASH enhanced thrombin and fibrin formation while reducing coagulation time. The mixture of IL-6 and TNF-a triggered the release of NETs in the plasma, and NETs exerted cytotoxic effects on endothelial cells.

CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY (2022)

Review Immunology

Neutrophils in cancer: heterogeneous and multifaceted

Catherine C. Hedrick et al.

Summary: Neutrophils have emerged as important regulators of cancer, revealing their diverse and plastic contributions in tumor development and growth, influencing positively and negatively depending on time, place, and disease context. Their functional importance in cancer has been overlooked due to their short-lived, terminally differentiated, and non-proliferative characteristics, but recent studies have led to a paradigm shift in understanding their roles.

NATURE REVIEWS IMMUNOLOGY (2022)

Article Immunology

Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases

Renato G. S. Chirivi et al.

Summary: The study demonstrated that therapeutic anti-citrullinated protein antibody can inhibit NET release, reduce tissue damage, and potentially serve as a drug candidate for NET-mediated inflammatory diseases.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

Article Hematology

miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis

Ana B. Arroyo et al.

Summary: This study investigated the impact and mechanisms of miR-146a deficiency on NETosis. miR-146a(-/-) mice showed increased NETosis in both atherosclerosis and acute inflammation models. miR-146a deficiency resulted in aged, hyperreactive, and pro-inflammatory neutrophils in the circulation of mice, which were more prone to form NET.

HAEMATOLOGICA (2021)

Article Cardiac & Cardiovascular Systems

Endotoxinemia Accelerates Atherosclerosis Through Electrostatic Charge-Mediated Monocyte Adhesion

Ariane Schumski et al.

Summary: Acute infection increases the risk of cardiovascular complications, with lipopolysaccharide playing a role in accelerating vascular inflammation through the activation of circulating immune cells. Histone H2a associated with NETs is shown to mediate charge-dependent monocyte adhesion and accelerate atherosclerosis during endotoxinemia.

CIRCULATION (2021)

Article Endocrinology & Metabolism

Peptidylarginine Deiminase Inhibition Prevents Diabetes Development in NOD Mice

Fernanda M. C. Sodre et al.

Summary: In this study, systemic inhibition of peptidylarginine deiminases (PADs) through BB-Cl-amidine treatment prevented diabetes development in NOD mice by reducing citrullination levels in the pancreas, decreasing circulating autoantibody titers, and reducing neutrophil extracellular trap formation. Additionally, the treatment induced a shift in cytokine production and increased regulatory T cell frequency. This highlights the potential of PAD inhibition for treating autoimmune diseases like type 1 diabetes.

DIABETES (2021)

Article Multidisciplinary Sciences

Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis

Kotaro Matsumoto et al.

Summary: Platelets play a key role in the pathogenesis of AAV by enhancing NETs formation through TLR9 signaling and CXCL4 release.

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Review Biochemistry & Molecular Biology

Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development

Anjali Trivedi et al.

Summary: Chronic obstructive pulmonary disease (COPD) is a significant global concern due to its morbidity, mortality, and economic burden. Neutrophil extracellular traps (NETs) play a crucial role in COPD, with excessive formation contributing to tissue destruction, impaired pulmonary function, and disease progression. Understanding the regulatory mechanisms of NET formation is essential for managing COPD and controlling disease exacerbations.

BIOMEDICINES (2021)

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Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223-enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis

Yong He et al.

Summary: This study reveals that the elevation of miR-223 in hepatocytes is due to preferential uptake of miR-223-enriched EVs released from neutrophils and other cells, mediated by LDLR and APOE expression. The internalized EV-derived miR-223 acts to inhibit hepatic inflammatory and fibrogenic gene expression, thereby limiting the progression of NASH.

JOURNAL OF CLINICAL INVESTIGATION (2021)

Article Immunology

Triggering Receptor Expressed on Myeloid Cells-1 Agonist Regulates Intestinal Inflammation via Cd177+ Neutrophils

Dong Hyuk Seo et al.

Summary: α-TREM-1 antibody alleviates colitis by modulating neutrophil function, clearing pathogens, protecting the intestinal barrier, and rebalancing the microbiota.

FRONTIERS IN IMMUNOLOGY (2021)

Review Immunology

Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different MO

Michele Fresneda Alarcon et al.

Summary: Dysregulated neutrophil activation plays a significant role in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, contributing to inflammation and autoantibody production in both autoimmune diseases.

FRONTIERS IN IMMUNOLOGY (2021)

Article Respiratory System

Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and Haemophilus infection in COPD

Sofia Winslow et al.

Summary: The study identified a subset of COPD patients with IL-6TS pathway activation, characterized by persistent neutrophilic inflammation, impaired respiratory function, and increased nitrite levels in lung tissue, suggesting that chronic colonization with Haemophilus may be a driving force for these patients.

EUROPEAN RESPIRATORY JOURNAL (2021)

Review Biochemistry & Molecular Biology

Cross-Talk among Polymorphonuclear Neutrophils, Immune, and Non-Immune Cells via Released Cytokines, Granule Proteins, Microvesicles, and Neutrophil Extracellular Trap Formation: A Novel Concept of Biology and Pathobiology for Neutrophils

Chang-Youh Tsai et al.

Summary: Polymorphonuclear neutrophils (PMNs) are not only professional phagocytic and acute inflammatory cells, but also exhibit many important biological functions, such as cytokine production, exosome release, and modulation of immune responses in surrounding cells.

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Targeting inflammation in atherosclerosis - from experimental insights to the clinic

Oliver Soehnlein et al.

Summary: Inflammation plays a substantial role in atherosclerosis and targeting inflammatory pathways could provide a promising new avenue to prevent and treat the disease. Clinical studies have shown that modulation of inflammation can help prevent the clinical complications of atherosclerosis. Refining strategies for combatting inflammation in the disease is crucial for further progress in managing atherosclerotic risk.

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The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments

Ricardo Grieshaber-Bouyer et al.

Summary: Neutrophils exhibit a single developmental spectrum, ranging from immature pre-neutrophils in the bone marrow to mature neutrophils in the blood and spleen. Inflammation affects neutrophil transcriptional states, leading to varying transcriptional activities at different sites.

NATURE COMMUNICATIONS (2021)

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The Relationship between Hepatic Myeloid-Derived Suppressor Cells and Clinicopathological Parameters in Patients with Chronic Liver Disease

Zhijia Zhou et al.

Summary: MDSCs play a significant role in chronic liver disease and their expression is closely related to clinical characteristics, serving as a potential indicator for disease activity and liver fibrosis progression.

BIOMED RESEARCH INTERNATIONAL (2021)

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Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps

Wanfa Dong et al.

Summary: Oral administration of ALG-SNase can reduce intestinal NET levels in UC mice, alleviate clinical colitis and tissue inflammation, and decrease intestinal permeability. Furthermore, SNase nanoparticles regulate the expression levels of proinflammatory cytokines, suggesting a potential therapeutic role for UC treatment.

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Peptidylarginine Deiminase 4 as a Possible Biomarker of Plaque Instability in Carotid Artery Stenosis

Koji Shimonaga et al.

Summary: The study revealed that carotid plaques with unstable features had high levels of PAD4 in patients with carotid artery stenosis, and the neutrophil to lymphocyte ratio in peripheral blood may serve as a biomarker for vulnerable plaques. Understanding the role of NETs could help clarify factors that contribute to the instability of carotid plaques.

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Associations of NETs with inflammatory risk and atherosclerotic severity in ST-segment elevation myocardial infarction

Jinying Zhou et al.

Summary: This study aimed to investigate the association between NETs in coronary thrombus and risk profile of STEMI patients, finding that patients in the high NETs group had higher levels of high-sensitivity C reactive protein and increased NETs in aspirated coronary thrombus were associated with more elevated inflammation but less advanced atherosclerosis.

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Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation

Suzanne H. Bongers et al.

Summary: Neutrophil phenotypes exhibit changes in disease states, with acute inflammation showing more heterogeneity and chronic inflammation not leading to increases in specific neutrophil subsets. The dynamics of neutrophil subsets in various inflammatory conditions contribute to our understanding of the role of neutrophils in health and disease.

FRONTIERS IN IMMUNOLOGY (2021)

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Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype

Carlos Blanco-Camarillo et al.

Summary: The article discusses the different phenotypes and functional states of neutrophils in healthy and pathological conditions, with a focus on the presence and cellular functions of low-density neutrophils (LDN) in the blood of healthy individuals.

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The Enigma of Low-Density Granulocytes in Humans: Complexities in the Characterization and Function of LDGs during Disease

Brittany G. Seman et al.

Summary: LDGs have been identified as important immune cells during healthy and disease states, but their classification and functional standards have made their identification and isolation challenging. Most research has focused on adult cells and subjects, leaving uncertainty surrounding younger populations, especially vulnerable neonatal groups.

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Metabolic Plasticity of Neutrophils: Relevance to Pathogen Responses and Cancer

Thomas Rogers et al.

Summary: The article discusses the role of neutrophils in fighting pathogens and cancer cells, as well as the role of tumor-associated neutrophils (TANs) in tumor development and how targeting TAN metabolism can enhance cancer immunotherapy.

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Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD

Sanooj Soni et al.

Summary: This study comprehensively evaluated different MV populations in BALF and plasma of COPD patients, finding that BALF neutrophil-derived MVs were uniquely correlated with several key functional and clinically relevant disease severity indexes. This suggests the potential of BALF neutrophil MVs as a COPD biomarker that links intra-alveolar neutrophil activation with clinical severity/outcome.

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Neutrophil Extracellular Traps Induce Intestinal Damage and Thrombotic Tendency in Inflammatory Bowel Disease

Tao Li et al.

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Changes in innate and adaptive immunity over the first year after the onset of type 1 diabetes

Adam Klocperk et al.

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Interleukin-22 Ameliorates Neutrophil-Driven Nonalcoholic Steatohepatitis Through Multiple Targets

Seonghwan Hwang et al.

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The Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation

Anastasia Poznyak et al.

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Neutrophils as regulators of cardiovascular inflammation

Carlos Silvestre-Roig et al.

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Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium

Ingrid Gomez et al.

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Circadian Features of Neutrophil Biology

Alejandra Aroca-Crevillen et al.

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Transient Intermittent Hyperglycemia Accelerates Atherosclerosis by Promoting Myelopoiesis

Michelle C. Flynn et al.

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Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)

Mirre De Bondt et al.

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MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease

Tao Zhang et al.

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Anti-Apolipoprotein A-1 IgG Influences Neutrophil Extracellular Trap Content at Distinct Regions of Human Carotid Plaques

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Brendan M. Everett et al.

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The Atlas of Inflammation Resolution (AIR)

Charles N. Serhan et al.

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Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019 Update From the GBD 2019 Study

Gregory A. Roth et al.

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Chronic Inflammation in Non-Alcoholic Steatohepatitis: Molecular Mechanisms and Therapeutic Strategies

Carmelo Luci et al.

FRONTIERS IN ENDOCRINOLOGY (2020)

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NETosis contributes to the pathogenes of diabetes and its complications

Rachel Njeim et al.

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Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD

Mike Lonergan et al.

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Neutrophil-macrophage cooperation and its impact on tissue repair

Tiffany Bouchery et al.

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Neutrophil Extracellular Traps Sustain Inflammatory Signals in Ulcerative Colitis

Vincenzo Dinallo et al.

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Neutrophils in Rheumatoid Arthritis: Breaking Immune Tolerance and Fueling Disease

Liam J. O'Neil et al.

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Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia

Jose Perdomo et al.

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CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis

Lucie Knabe et al.

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Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice

Taylor S. Cohen et al.

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Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death

Carlos Silvestre-Roig et al.

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Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation

Yasuharu Watanabe et al.

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More friend than foe: the emerging role of neutrophils in tissue repair

Moritz Peiseler et al.

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The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis

Zobair M. Younossi et al.

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Pro-Angiogenic Macrophage Phenotype to Promote Myocardial Repair

Bartolo Ferraro et al.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2019)

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Platelet-Neutrophil Crosstalk in Atherothrombosis

Joachim Pircher et al.

THROMBOSIS AND HAEMOSTASIS (2019)

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Neutrophil Diversity in Health and Disease

Carlos Silvestre-Roig et al.

TRENDS IN IMMUNOLOGY (2019)

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Effect of weight loss on neutrophil resolvins in the metabolic syndrome

A. Barden et al.

PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS (2019)

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Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis

Franziska Herster et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Neutrophil Heterogeneity in Cancer: From Biology to Therapies

Pacome Lecot et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Knockout of neutrophil elastase protects against western diet induced nonalcoholic steatohepatitis in mice by regulating hepatic ceramides metabolism

Jin Chen et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2019)

Article Multidisciplinary Sciences

Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus

Pragnesh Mistry et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Review Immunology

Misunderstandings Between Platelets and Neutrophils Build in Chronic Inflammation

Giuseppe A. Ramirez et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

Deepak L. Bhatt et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Chronic inflammation in the etiology of disease across the life span

David Furman et al.

NATURE MEDICINE (2019)

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Cell type-specific immune phenotypes predict loss of insulin secretion in new-onset type 1 diabetes

Matthew J. Dufort et al.

JCI INSIGHT (2019)

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Mouse Models for Atherosclerosis Research-Which Is My Line?

Sara Oppi et al.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2019)

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Neutrophil elastase as a biomarker for bacterial infection in COPD

Samantha J. Thulborn et al.

RESPIRATORY RESEARCH (2019)

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CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD

Guangxi Zhou et al.

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Global aetiology and epidemiology of type 2 diabetes mellitus and its complications

Yan Zheng et al.

NATURE REVIEWS ENDOCRINOLOGY (2018)

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Partners in crime: neutrophils and monocytes/macrophages in inflammation and disease

Kathryn Prame Kumar et al.

CELL AND TISSUE RESEARCH (2018)

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Roles of PAD4 and NETosis in Experimental Atherosclerosis and Arterial Injury Implications for Superficial Erosion

Gregory Franck et al.

CIRCULATION RESEARCH (2018)

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Netting Neutrophils Activate Autoreactive B Cells in Lupus

Nicolas Gestermann et al.

JOURNAL OF IMMUNOLOGY (2018)

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LANCET (2018)

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NATURE IMMUNOLOGY (2018)

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Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation

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INNATE IMMUNITY (2018)

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Neutrophil elastase and myeloperoxidase mRNA expression in overweight and obese subjects

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MOLECULAR BIOLOGY REPORTS (2018)

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Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis

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Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes

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Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes

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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Dmitry I. Gabrilovich

CANCER IMMUNOLOGY RESEARCH (2017)

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Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria

Florian Gaertner et al.

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Oral delivery of staphylococcal nuclease by Lactococcus lactis prevents type 1 diabetes mellitus in NOD mice

Junchao Lang et al.

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY (2017)

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Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice

Rongying Ou et al.

ENDOCRINE (2017)

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Neutrophils as protagonists and targets in chronic inflammation

Oliver Soehnlein et al.

NATURE REVIEWS IMMUNOLOGY (2017)

Article Pharmacology & Pharmacy

Increased ratio of neutrophil elastase to α1-antitrypsin is closely associated with liver inflammation in patients with nonalcoholic steatohepatitis

Shufei Zang et al.

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY (2016)

Article Biochemistry & Molecular Biology

p38γ and p38δ reprogram liver metabolism by modulating neutrophil infiltration

Barbara Gonzalez-Teran et al.

EMBO JOURNAL (2016)

Review Immunology

Human neutrophils in the saga of cellular heterogeneity: insights and open questions

Patrizia Scapini et al.

IMMUNOLOGICAL REVIEWS (2016)

Article Immunology

The responses of macrophages in interaction with neutrophils that undergo NETosis

Daigo Nakazawa et al.

JOURNAL OF AUTOIMMUNITY (2016)

Review Immunology

The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes

James A. Pearson et al.

JOURNAL OF AUTOIMMUNITY (2016)

Article Biochemistry & Molecular Biology

Activation of Proteinase 3 Contributes to Nonalcoholic Fatty Liver Disease and Insulin Resistance

Erik J. M. Toonen et al.

MOLECULAR MEDICINE (2016)

Review Medicine, General & Internal

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Odile Wera et al.

JOURNAL OF CLINICAL MEDICINE (2016)

Article Critical Care Medicine

CXCR2 Antagonist MK-7123 A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease

Stephen I. Rennard et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2015)

Article Biochemistry & Molecular Biology

Neutrophils Play a Crucial Role in the Early Stage of Nonalcoholic Steatohepatitis via Neutrophil Elastase in Mice

Shufei Zang et al.

CELL BIOCHEMISTRY AND BIOPHYSICS (2015)

Article Respiratory System

Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence

Antoine Guillon et al.

EUROPEAN RESPIRATORY JOURNAL (2015)

Article Immunology

LL-37 Immunomodulatory Activity during Mycobacterium tuberculosis Infection in Macrophages

Flor Torres-Juarez et al.

INFECTION AND IMMUNITY (2015)

Review Medicine, General & Internal

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Lifeng Wang et al.

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Article Cell Biology

Neutrophil elastase promotes myofibroblast differentiation in lung fibrosis

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Diabetes primes neutrophils to undergo NETosis, which impairs wound healing

Siu Ling Wong et al.

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Neutrophil extracellular traps promote differentiation and function of fibroblasts

Akrivi Chrysanthopoulou et al.

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Neutrophils scan for activated platelets to initiate inflammation

Vinatha Sreeramkumar et al.

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Reduction of Circulating Neutrophils Precedes and Accompanies Type 1 Diabetes

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IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis

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Late Intervention with a Myeloperoxidase Inhibitor Stops Progression of Experimental Chronic Obstructive Pulmonary Disease

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Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase

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Host Defense Peptide LL-37 Selectively Reduces Proinflammatory Macrophage Responses

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The immune system in atherosclerosis

Goran K. Hansson et al.

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Neutrophil transmigration triggers repair of the lung epithelium via β-catenin signaling

Rachel L. Zemans et al.

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Lynn M. Crosby et al.

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