Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?

Rosales, Carlos

doi:10.3389/fphys.2018.00113

Cited by 1,334Neutrophil, Myeloperoxidase and Oxidative MechanismsImmune cells in cancerInflammation biomarkers and pathways

Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?

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Rosales, Carlos·2018·Frontiers in Physiology

DOI 10.3389/fphys.2018.00113PMC PMC5826082

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Abstract

Neutrophils are the most abundant leukocytes in the circulation, and have been regarded as first line of defense in the innate arm of the immune system. They capture and destroy invading microorganisms, through phagocytosis and intracellular degradation, release of granules, and formation of neutrophil extracellular traps after detecting pathogens. Neutrophils also participate as mediators of inflammation. The classical view for these leukocytes is that neutrophils constitute a homogenous population of terminally differentiated cells with a unique function. However, evidence accumulated in recent years, has revealed that neutrophils present a large phenotypic heterogeneity and functional versatility, which place neutrophils as important modulators of both inflammation and immune responses. Indeed, the roles played by neutrophils in homeostatic conditions as well as in pathological inflammation and immune processes are the focus of a renovated interest in neutrophil biology. In this review, I present the concept of neutrophil phenotypic and functional heterogeneity and describe several neutrophil subpopulations reported to date. I also discuss the role these subpopulations seem to play in homeostasis and disease.

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Anti-inflammatory N2 neutrophils are polarized by IL-8 and switch their secretomes to TGF-β, IL-10, and SDF-1α, which in turn promotes Tregs and alternatively activated M2 macrophages.
“Anti-inflammatory N2 neutrophils are polarized by IL-8 and switch their secretomes to TGF-β, IL-10, and SDF-1α which in turn promotes Tregs and alternatively activated M2 macrophages [19, 39–41].”
From Osteoimmunology of Fracture Healing. (2024) · cites this paper as [39]
The ‘Neutrophil subpopulations in cancer’ section describes N2 tumor-associated neutrophils as immunosuppressive, but associates their N2 phenotype with TGF-β in tumor-bearing mice, not IL-8 polarization. The ‘Neutrophil subpopulations in inflammation’ section says a different subset, PMN-2, produces IL-10 and alternatively activates macrophages. Neither passage supports the claimed N2 secretome of TGF-β, IL-10, and SDF-1α or its promotion of Tregs. (LLM, conf=0.87)
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Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice
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Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes
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Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin
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Sodium Overload and Water Influx Activate the NALP3 Inflammasome
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Prognostic Value of Intratumoral Neutrophils in Advanced Gastric Carcinoma in a High-Risk Area in Northern Italy
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Reverse Migration of Neutrophils: Where, When, How, and Why?
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Neutrophil Extracellular Traps and Endothelial Dysfunction in Atherosclerosis and Thrombosis
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Revision of the Human Hematopoietic Tree: Granulocyte Subtypes Derive from Distinct Hematopoietic Lineages
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Neutrophils Transport Antigen from the Dermis to the Bone Marrow, Initiating a Source of Memory CD8+ T Cells
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Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy
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Human neutrophils switch to an activated phenotype after homing to the lung irrespective of inflammatory disease
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Cathepsin B inhibition prevents trypsinogen activation and reduces pancreatitis severity
van Acker, G. J. D., Saluja, A. K., Bhagat, L., Singh, V. P., Song, A. M., & Steer, M. L. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00363.2001 · Cited by 154 · see citing works
The Pathophysiological Role of Neutrophil Extracellular Traps in Inflammatory Diseases
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The kinship of neutrophils and granulocytic myeloid-derived suppressor cells in cancer: Cousins, siblings or twins?
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Neutrophil‐Related Gene Expression and Low‐Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Grayson, P. C., Carmona‐Rivera, C., Xu, L., Lim, N., Gao, Z., Asare, A. L., Specks, U., Stone, J. H., Seo, P., Spiera, R., et al. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39153 · Cited by 143 · see citing works
The diversity of circulating neutrophils in cancer
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IL-1R type I-dependent hemopoietic stem cell proliferation is necessary for inflammatory granulopoiesis and reactive neutrophilia
Ueda, Y., Cain, D. W., Kuraoka, M., Kondo, M., & Kelsoe, G. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803961 · Cited by 138 · cited 2× · see citing works
“inflammation, IL-1 can also stimulate neutrophil production through the IL-17-G-CSF axis (Ueda et al., 2009), and neutrophils themselves create a positive loop for neutrophil recruitment.”
Background
Complexity and challenges in defining myeloid-derived suppressor cells
Damuzzo, V., Pinton, L., Desantis, G., Solito, S., Marigo, I., Bronte, V., & Mandruzzato, S. (2014) · Cytometry Part B Clinical Cytometry · doi:10.1002/cytob.21206 · Cited by 136 · see citing works
Does the presence of crystal arthritis rule out septic arthritis?
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Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation
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DAMPs and NETs in Sepsis
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Effects of Omega-3 Fatty Acids on Immune Cells
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The Role of Inflammation in the Pathogenesis of Osteoarthritis
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Neutrophil Diversity in Health and Disease
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Neutrophil-to-lymphocyte ratio and mortality in the United States general population
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Myeloid Cell-Derived Arginase in Cancer Immune Response
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Percolation on complex networks: Theory and application
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Self-citation
The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives
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BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils
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An Attempt to Polarize Human Neutrophils Toward N1 and N2 Phenotypes in vitro
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The functional crosstalk between myeloid-derived suppressor cells and regulatory T cells within the immunosuppressive tumor microenvironment
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Multiple Roles for Chemokines in Neutrophil Biology
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Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O.
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Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth
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GM-CSF: A Double-Edged Sword in Cancer Immunotherapy
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Invited review: The influence of immune activation on transition cow health and performance—A critical evaluation of traditional dogmas
Horst, E. A., Kvidera, S. K., & Baumgard, L. H. (2021) · Journal of Dairy Science · doi:10.3168/jds.2021-20330 · Cited by 268 · see citing works
Inflammation and Cell Death of the Innate and Adaptive Immune System during Sepsis
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Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems
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Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects
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Engineering Cell Membrane‐Based Nanotherapeutics to Target Inflammation
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The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens
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Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease
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Neutrophils: from IBD to the gut microbiota
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Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice—Which to Use Regarding Disease Outcomes?
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Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes
Vecchio, F., Buono, N. L., Stabilini, A., Nigi, L., Dufort, M. J., Geyer, S. M., Rancoita, P. M. V., Cugnata, F., Mandelli, A., Valle, A., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.122146 · Cited by 219 · see citing works
Neutrophils as potential therapeutic targets in hepatocellular carcinoma
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Aseptic and septic prosthetic joint loosening: Impact of biomaterial wear on immune cell function, inflammation, and infection
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Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond
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Cell Membrane-Coated Mimics: A Methodological Approach for Fabrication, Characterization for Therapeutic Applications, and Challenges for Clinical Translation
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Extracellular CIRP (eCIRP) and inflammation
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Hypoxia, Metabolism and Immune Cell Function
Krzywińska, E., & Stockmann, C. (2018) · Biomedicines · doi:10.3390/biomedicines6020056 · Cited by 207 · see citing works
Deep insight into cytokine storm: from pathogenesis to treatment
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Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease
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Adenosine signaling and the immune system: When a lot could be too much
Antonioli, L., Fornai, M., Blandizzi, C., Pacher, P., & Haskó, G. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.04.006 · Cited by 193 · see citing works
Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality
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Understanding the role of neutrophils in chronic inflammatory airway disease
Jasper, A. E., McIver, W. J., Sapey, E., & Walton, G. (2019) · F1000Research · doi:10.12688/f1000research.18411.1 · Cited by 189 · see citing works
Neutrophils in the Tumor Microenvironment
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Cell membrane-derived vesicles for delivery of therapeutic agents
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Adenosine and Inflammation: Here, There and Everywhere
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Circulating tumor cell-blood cell crosstalk: Biology and clinical relevance
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Harnessing strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns
Cai, Y., Chen, K., Liu, C., & Qu, X. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.04.019 · Cited by 169 · see citing works
A census of the lung: CellCards from LungMAP
Sun, X., Perl, A. T., Li, R., Bell, S. M., Sajti, E., Kalinichenko, V. V., Kalin, T. V., Misra, R. S., Deshmukh, H. S., Clair, G., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.11.007 · Cited by 157 · see citing works
Role of immune cells in hypertension
Caillon, A., Paradis, P., & Schiffrin, E. L. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14427 · Cited by 163 · see citing works
Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer
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Molecular and Cellular Mechanisms of Action of Cannabidiol
Naya, N. M., Kelly, J., Corna, G., Golino, M., Abbate, A., & Toldo, S. A. (2023) · Molecules · doi:10.3390/molecules28165980 · Cited by 158 · see citing works
Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review
Frank, D., Gruenbaum, B. F., Zlotnik, A. A., Semyonov, M., Frenkel, A., & Boyko, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315114 · Cited by 154 · see citing works
The pathogenesis of systemic lupus erythematosus: Harnessing big data to understand the molecular basis of lupus
Catalina, M. D., Owen, K. A., Labonte, A. C., Grammer, A. C., & Lipsky, P. E. (2019) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.102359 · Cited by 145 · see citing works
Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies
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Background
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Self-citation

Authors: Rosales, C.
Affiliations: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (MX)
Corresponding author: Rosales, Carlos
ORCID: Rosales, Carlos
Venue: Frontiers in Physiology
Publisher: Frontiers Media SA
Published: 2018-02-20
Volume: 9
Pages: 113-113
ISSN: 1664-042X (ISSN-L)
DOI: 10.3389/fphys.2018.00113
PMC: PMC5826082
OpenAlex: W2792366526
Cited by: 1,334
References: 206
Citations by year: 2026: 104 · 2025: 162 · 2024: 207 · 2023: 236 · 2022: 196 · 2021: 196 · 2020: 142 · 2019: 67 · 2018: 22 · 2017: 1 · 2016: 1
FWCI: 10.79
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: Frontiers in Physiology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Consejo Nacional de Ciencia y Tecnología (254434)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords: neutrophils, neutrophil heterogeneity, neutrophil subpopulations, inflammation, innate immunity, neutrophil extracellular traps, phagocytosis, granule release, immune homeostasis

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Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?

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