Neutrophil chemoattractant receptors in health and disease: Double-edged swords

Metzemaekers, Mieke; Gouwy, Mieke; Proost, Paul

doi:10.1038/s41423-020-0412-0

Cited by 572Chemokine receptors and signalingNeutrophil, Myeloperoxidase and Oxidative MechanismsInflammation biomarkers and pathways

Neutrophil chemoattractant receptors in health and disease: Double-edged swords

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Metzemaekers, Mieke, Gouwy, Mieke, Proost, Paul·2020·Cellular & Molecular Immunology

DOI 10.1038/s41423-020-0412-0PMC PMC7192912

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Abstract

Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease. Depending on the (patho)physiological context, specific chemoattractant receptors may be up- or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences, thus opening new windows for the identification of disease biomarkers and potential drug targets.

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In the presence of pathogens, host cells such as monocytes and macrophages secrete inflammatory and neutrophil chemoattractant mediators such as LTB4, IL-8, and CXCL6/GCP-2, which bind to specific receptors on the neutrophil surface.
“In the presence of pathogens, different host cells (such as monocytes and macrophages) secrete inflammatory and neutrophil chemoattractant mediators (such as the leukotriene LTB4 involved in inflammation, the interleukin IL-8, and the chemokine CXCL6, a small cytokine belonging to the CXC chemokine family, also known as granulocyte chemotactic protein 2 GCP-2) which bind to specific receptors on”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [215]

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“Furthermore, the absence of CXCR2 was associated with delayed experimental cutaneous wound healing in mice, supporting the notion that neutrophils are critically involved in tissue repair.(166) Neutrophils within the tumor microenvironment may be classified into protumoral and antitumoral phenotypes,(167) and the cont…”
Background
C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid
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The Expression of Formyl Peptide Receptor 1 is Correlated with Tumor Invasion of Human Colorectal Cancer
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Absence of formyl peptide receptor 1 causes endometriotic lesion regression in a mouse model of surgically-induced endometriosis
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EARLY EXPRESSION CHANGES OF COMPLEMENT REGULATORY PROTEINS AND C5a RECEPTOR (CD88) ON LEUKOCYTES AFTER MULTIPLE INJURY IN HUMANS
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An atypical addition to the chemokine receptor nomenclature: IUPHAR Review 15
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The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention
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Neutrophil extracellular traps in homeostasis and disease
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High-Resolution Single-Cell Atlas Reveals Diversity and Plasticity of Tissue-Resident Neutrophils in Non-Small Cell Lung Cancer
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Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity
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Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
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Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity
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Neutrophil diversity and function in health and disease
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Neutrophils as potential therapeutic targets in hepatocellular carcinoma
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Studying Neutrophil Function in vitro: Cell Models and Environmental Factors
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The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD
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Self-sustaining IL-8 loops drive a prothrombotic neutrophil phenotype in severe COVID-19
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Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy
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Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis
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Chemokines and eicosanoids fuel the hyperinflammation within the lungs of patients with severe COVID-19
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Exosomal PGE2 from M2 macrophages inhibits neutrophil recruitment and NET formation through lipid mediator class switching in sepsis
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Authors: Metzemaekers, M., Gouwy, M., & Proost, P.
Affiliations: KU Leuven (BE)
Corresponding author: Proost, Paul
ORCID: Metzemaekers, Mieke
Gouwy, Mieke
Proost, Paul
Venue: Cellular & Molecular Immunology
Publisher: Springer Science and Business Media LLC
Published: 2020-04-01
Volume: 17
Issue: 5
Pages: 433-450
ISSN: 1672-7681 (ISSN-L)
2042-0226
DOI: 10.1038/s41423-020-0412-0
PMC: PMC7192912
OpenAlex: W3014824156
Cited by: 570
References: 246
Citations by year: 2026: 75 · 2025: 124 · 2024: 115 · 2023: 110 · 2022: 94 · 2021: 43 · 2020: 9
FWCI: 6.87
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Cellular and Molecular Immunology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Lirias (submittedVersion, other-oa)
Funders: Onderzoeksraad, KU Leuven (C16/17/010)
Fonds Wetenschappelijk Onderzoek (G.0808.18N)
EC | Horizon 2020 Framework Programme (779295)
Rega Foundation
M.M. obtained a PhD fellowship supported by the L’Oréal-UNESCO for Women in Science initiative and the FWO-Vlaanderen
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords: neutrophils, chemoattractant receptors, G protein-coupled receptors, atypical chemokine receptors, formyl peptides, anaphylatoxins, chemokines, neutrophil trafficking, neutrophil maturation, inflammation resolution, tissue repair, disease biomarkers, therapeutic target
MeSH terms: Animals, Chemotactic Factors, Disease, Health, Humans, Neutrophils, Signal Transduction, Receptors, Formyl Peptide

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Neutrophil chemoattractant receptors in health and disease: Double-edged swords

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