ArticleThe Journal of allergy and clinical immunology2019
Novel peptide nanoparticle-biased antagonist of CCR3 blocks eosinophil recruitment and airway hyperresponsiveness.
Article in The Journal of allergy and clinical immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- Investigating the Effects of a CCR3 Antagonist and SP-A Eosinophil Suppressor Tetrapeptide-Transduced Mesenchymal Stem Cells in Allergic Asthma.Applied biochemistry and biotechnology · 2026Article
- Dermal fibroblasts respond to IL-4 and IL-13 and promote T cell recruitment in atopic dermatitis.The Journal of clinical investigation · 2026Article
- The CCL11-CCR3 Axis Regulates the Aggravation of Neuroinflammation in Astrocytic Necroptosis After Cerebral Ischemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Bone marrow CCR3 dictates eosinophil lineage commitment of CD34⁺ progenitors to orchestrate allergic rhinitis: A composite study.PloS one · 2026Article
- Expanding the Spectrum: A Rare Case of Morquio Syndrome With Bronchial Asthma and Seizure Disorder.Clinical case reports · 2025Article
- Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation.Pathogens (Basel, Switzerland) · 2025Article
- Innovative approaches to asthma treatment: harnessing nanoparticle technology.Discover nano · 2025Review
- Eosinophils in inflammatory bowel disease pathogenesis: an ROS-centric view.Frontiers in allergy · 2025Article
- Targeting Multiple Pathophysiological Axes in COPD: Nanomaterial Advances.International journal of nanomedicine · 2025Review
- Article
- Sphingosine kinase 1-specific inhibitor PF543 reduces goblet cell metaplasia of bronchial epithelium in an acute asthma model.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- The airway neuro-immune axis as a therapeutic target in allergic airway diseases.Respiratory research · 2024Review
- An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma.Clinical and experimental medicine · 2023Review
- Mechanistic Insights into Eosinophilic Esophagitis: Therapies Targeting Pathophysiological Mechanisms.Cells · 2023Review
- Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma.International journal of molecular sciences · 2023Review
- Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Development of tolerance to chemokine receptor antagonists: current paradigms and the need for further investigation.Frontiers in immunology · 2023Review
- Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells.Cell discovery · 2022Article
- Potent CCR3 Receptor Antagonist, SB328437, Suppresses Colonic Eosinophil Chemotaxis and Inflammation in theInternational journal of molecular sciences · 2022Article
- Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3.Cell discovery · 2022Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundChemokine signaling through CCR3 is a key regulatory pathway for eosinophil recruitment into tissues associated with allergic inflammation and asthma. To date, none of the CCR3 antagonists have shown efficacy in clinical trials. One reason might be their unbiased mode of inhibition that prevents receptor internalization, leading to drug tolerance.
objectiveWe sought to develop a novel peptide nanoparticle CCR3 inhibitor (R321) with a biased mode of inhibition that would block G protein signaling but enable or promote receptor internalization.
methodsSelf-assembly of R321 peptide into nanoparticles and peptide binding to CCR3 were analyzed by means of dynamic light scattering and nuclear magnetic resonance. Inhibitory activity on CCR3 signaling was assessed in vitro by using flow cytometry, confocal microscopy, and Western blot analysis in a CCR3
resultsR321 self-assembles into nanoparticles and binds directly to CCR3, altering receptor function. Half-maximal inhibitory concentration values for eotaxin-induced chemotaxis of blood eosinophils are in the low nanomolar range. R321 inhibits only the early phase of extracellular signal-regulated kinase 1/2 activation and not the late phase generally associated with β-arrestin recruitment and receptor endocytosis, promoting CCR3 internalization and degradation. In vivo R321 effectively blocks eosinophil recruitment into the blood, lungs, and airways and prevents airway hyperresponsiveness in a mouse eosinophilic asthma model.
conclusionsR321 is a potent and selective antagonist of the CCR3 signaling cascade. Inhibition through a biased mode of antagonism might hold significant therapeutic promise by eluding the formation of drug tolerance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.