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Neutrophil chemoattractant receptors in health and disease: double-edged swords
Open accessAbstract
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, 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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“These components then interact through speci fi c signaling pathways, orchestrating a cascade of responses that regulate both anti-in fl ammatory and pro-in fl ammatory mechanisms, maintaining homeostatic balance within the human body (75).”
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“22 Any dysregulation in the spatiotemporal expression of this chemokine pattern would 1600065x , 0 , D o w n l o a d e d fr o m h tt p s :// on li n e li b r a r y . w il e y . c o m / do i/ 10 .”
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“…or S1P; lysophosphatidic acid or LPA), complement anaphylatoxins (C3a and C5a with their receptors C3aR and C5aR) and formyl peptides ( e.g. , N-formyl-Met-Leu-Phe or fMLF with the receptors FPR1 and FPR2), all of which function by activating dedicated receptors that are coupled to G proteins [77].”
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“37 Our results suggest that 177 Lu- DOTA-2P(FAPI) 2 combined with α PD-L1 mAb immunotherapy-induced CXCL2 expression is responsible for recruiting antitumor neutrophils to the TME.”
Neutrophil trafficking to the site of infection requires Cpt1a-dependent fatty acid β-oxidation
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The Role of Neutrophils in Pregnancy, Term and Preterm Labour
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Innate immunity-modulating nanobiomaterials for controlling inflammation resolution
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Research Progress of Neutrophil-Mediated Drug Delivery Strategies for Inflammation-Related Disease
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Biopolymer-Based Wound Dressings with Biochemical Cues for Cell-Instructive Wound Repair
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“Upon inflammation initiation, platelets induce chemotaxis to bring in neutrophils which then commence phagocytosis of bacteria [139].”
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Staphylococcus aureus in Inflammation and Pain: Update on Pathologic Mechanisms
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Stress, neutrophils, and immunity: a dynamic interplay
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“Neutrophils possess surface receptors that recognize chemokines and other signaling molecules released during stress or tissue damage [27] .”
Active ingredients of traditional Chinese medicine for enhancing the effect of tumor immunotherapy
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Platelet signaling at the nexus of innate immunity and rheumatoid arthritis
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CXCL5 suppression recovers neovascularization and accelerates wound healing in diabetes mellitus
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Fast and furious: The neutrophil and its armamentarium in health and disease
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“receptors such as CCR1, CCR2, CCR3, CCR5, and CXCR3, which are usually not expressed by circulating neutrophils.(106) Stimulation with exogenous or endogenous inflammatory agents at the site of inflammation may induce additional phenotypical and functional changes.”
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Chu, Y.-T., Liao, M.-T., Tsai, K., Lu, K., & Hu, W. (2023) · Biomedicines · doi:10.3390/biomedicines11092384 · Cited by 32
“11 A summary of chemokine receptors and their associations with the framework of host immunological pathways are shown in Figures 3 and 4. important chemokine that targets neutrophils and activates them [102,103].”
CTC-neutrophil interaction: A key driver and therapeutic target of cancer metastasis
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Harnessing myeloid cells in cancer
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“…factor I (Cfi), involved in regulation of the complement cascade (Roversi et al., 2011); C-C motif chemokine ligand 3 (Ccl3), involved in monocyte/macrophage chemotaxis (Metzemaekers et al., 2020); and NCK-associated protein 1 like (Nckap1l), involved in neutrophil migration (Cook et al., 2020).”
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The Tumour Vasculature as a Target to Modulate Leucocyte Trafficking
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Intestinal organoids in coculture: redefining the boundaries of gut mucosa ex vivo modeling
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Lonicerae Japonicae Flos Attenuates Neutrophilic Inflammation by Inhibiting Oxidative Stress
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“Pathogen-associated molecular patterns (PAMPs) such as fMLF can activate neutrophils, resulting in a series of inflammatory responses, including degranulation (elastase release), respiratory burst (O2•− generation), chemotactic adhesion, and migration [32].”
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“In addition, leukocytes, including neutrophils, eosinophils, basophils, monocytes, and lymphocytes, can release antimicrobial substances until more specialized cells (macrophage) reach the site of inflammation where a more effective attack is launched.(28) However, recent study suggests that leukocytes are more sophis…”
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“Neutrophils are derived from myeloid progenitor cells commonly found in bone marrow and extramedullary tissues (e.g., spleen), and account for 50–70% of the total leukocytes in the peripheral blood of humans (only 10–25% in mice) [26].”
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“In the spinal nerve section model, the expression of TRPV1 mRNA is reduced in the axotomized ganglia, suggesting loss of trophic support after the injury (Michael and Priestley, 1999).”
Background
Metadata
- Authors
- Metzemaekers, M., Gouwy, M., & Proost, P.
- Affiliations
- KU Leuven (BE)
- Corresponding author
- Proost, Paul
- Venue
- Cellular & Molecular Immunology
- Published
- 2020-04-01
- Volume
- 17
- Issue
- 5
- Pages
- 433-450
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- 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
- 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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