CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells
Abstract Background IL‐33 is involved in allergic processes by promoting the release of various mast cell (MC) chemokines, including CCL2. However, it is yet unclear which specific cell type is primarily responsible for producing CCL2 during acute allergic reactions. This study aims to investigate t...
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Wiley
2025-02-01
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| Series: | Clinical and Translational Allergy |
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| Online Access: | https://doi.org/10.1002/clt2.70044 |
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| author | Maruša Rihar Rajia Bahri Vida Forstnerič Silvia Bulfone‐Paus Peter Korošec |
| author_facet | Maruša Rihar Rajia Bahri Vida Forstnerič Silvia Bulfone‐Paus Peter Korošec |
| author_sort | Maruša Rihar |
| collection | DOAJ |
| description | Abstract Background IL‐33 is involved in allergic processes by promoting the release of various mast cell (MC) chemokines, including CCL2. However, it is yet unclear which specific cell type is primarily responsible for producing CCL2 during acute allergic reactions. This study aims to investigate the role of IL‐33 in promoting CCL2 production in mast cells and assess the effect of MC‐derived CCL2 on basophil migration and endothelial permeability. Methods Human blood‐derived MCs (hMCs) were generated from peripheral blood precursors, passively sensitized with IgE, treated with IL‐33, and stimulated with anti‐IgE. The concentrations of nine cytokines known to influence immune cell chemotaxis (CCL2, CCL5, CCL11, MIP‐1α, IL‐8, IL‐10, IL‐13, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and vascular endothelial growth factor (VEGF) were assessed in the supernatants of hMCs. Subsequently, we investigated the impact of MC‐derived CCL2 on basophil migration in vitro, as well as its effect on endothelial monolayer permeability using human umbilical vein endothelial cells (HUVECs). Results Stimulation with anti‐IgE induced a significant release of CCL2, GM‐CSF, IL‐8 and VEGF from hMCs. Additionally, incubation with IL‐33 overnight increased the production of several cytokines. Mast cell‐derived CCL2 not only enhanced basophil migration in vitro but also increased endothelial monolayer permeability in HUVECs. The effect was reversed by a C–C chemokine receptor type 2 (CCR2) antagonist, indicating the involvement of CCL2 signaling through the CCR2 receptor. Conclusions IL‐33 induces the production of chemotactic cytokines in hMCs. Mast cell‐derived CCL2 plays an important role in basophil chemotaxis in vitro and affects endothelial monolayer permeability in the HUVEC model. |
| format | Article |
| id | doaj-art-c7ceb6c27cf7410bbcadc8b2e75b4150 |
| institution | DOAJ |
| issn | 2045-7022 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
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| series | Clinical and Translational Allergy |
| spelling | doaj-art-c7ceb6c27cf7410bbcadc8b2e75b41502025-08-20T03:12:24ZengWileyClinical and Translational Allergy2045-70222025-02-01152n/an/a10.1002/clt2.70044CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cellsMaruša Rihar0Rajia Bahri1Vida Forstnerič2Silvia Bulfone‐Paus3Peter Korošec4University Clinic of Respiratory and Allergic Diseases Golnik Golnik SloveniaLydia Becker Institute of Immunology and Inflammation Division of Musculoskeletal and Dermatological Sciences School of Biological Sciences University of Manchester Manchester UKDepartment of Synthetic Biology and Immunology National Institute of Chemistry Ljubljana SloveniaLydia Becker Institute of Immunology and Inflammation Division of Musculoskeletal and Dermatological Sciences School of Biological Sciences University of Manchester Manchester UKUniversity Clinic of Respiratory and Allergic Diseases Golnik Golnik SloveniaAbstract Background IL‐33 is involved in allergic processes by promoting the release of various mast cell (MC) chemokines, including CCL2. However, it is yet unclear which specific cell type is primarily responsible for producing CCL2 during acute allergic reactions. This study aims to investigate the role of IL‐33 in promoting CCL2 production in mast cells and assess the effect of MC‐derived CCL2 on basophil migration and endothelial permeability. Methods Human blood‐derived MCs (hMCs) were generated from peripheral blood precursors, passively sensitized with IgE, treated with IL‐33, and stimulated with anti‐IgE. The concentrations of nine cytokines known to influence immune cell chemotaxis (CCL2, CCL5, CCL11, MIP‐1α, IL‐8, IL‐10, IL‐13, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and vascular endothelial growth factor (VEGF) were assessed in the supernatants of hMCs. Subsequently, we investigated the impact of MC‐derived CCL2 on basophil migration in vitro, as well as its effect on endothelial monolayer permeability using human umbilical vein endothelial cells (HUVECs). Results Stimulation with anti‐IgE induced a significant release of CCL2, GM‐CSF, IL‐8 and VEGF from hMCs. Additionally, incubation with IL‐33 overnight increased the production of several cytokines. Mast cell‐derived CCL2 not only enhanced basophil migration in vitro but also increased endothelial monolayer permeability in HUVECs. The effect was reversed by a C–C chemokine receptor type 2 (CCR2) antagonist, indicating the involvement of CCL2 signaling through the CCR2 receptor. Conclusions IL‐33 induces the production of chemotactic cytokines in hMCs. Mast cell‐derived CCL2 plays an important role in basophil chemotaxis in vitro and affects endothelial monolayer permeability in the HUVEC model.https://doi.org/10.1002/clt2.70044basophil migrationCCL2endothelial monolayer permeabilityhuman mast cellsIL‐33 |
| spellingShingle | Maruša Rihar Rajia Bahri Vida Forstnerič Silvia Bulfone‐Paus Peter Korošec CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells Clinical and Translational Allergy basophil migration CCL2 endothelial monolayer permeability human mast cells IL‐33 |
| title | CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells |
| title_full | CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells |
| title_fullStr | CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells |
| title_full_unstemmed | CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells |
| title_short | CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells |
| title_sort | ccl2 c c chemokine receptor type 2 mediated interactions among mast cells basophils and endothelial cells |
| topic | basophil migration CCL2 endothelial monolayer permeability human mast cells IL‐33 |
| url | https://doi.org/10.1002/clt2.70044 |
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