CCL2/C–C chemokine receptor type 2-mediated interactions among mast cells, basophils, and endothelial cells

IF 4.6 2区医学 Q2 ALLERGY

Clinical and Translational Allergy Pub Date : 2025-02-23 DOI:10.1002/clt2.70044

Maruša Rihar, Rajia Bahri, Vida Forstnerič, Silvia Bulfone-Paus, Peter Korošec

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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.

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来源期刊

Clinical and Translational Allergy Immunology and Microbiology-Immunology

CiteScore

7.50

自引率

4.50%

发文量

117

审稿时长

12 weeks

期刊介绍： Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience. Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.