Cited by 571Chemokine receptors and signalingNeutrophil, Myeloperoxidase and Oxidative MechanismsInflammation biomarkers and pathways

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

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