Evaluation of the inhibitory effect of different molecular weights chitosan on MRGPRX2-mediated mast cell degranulation and the pseudo-allergic reaction.

IF 3 4区 医学 Q3 IMMUNOLOGY Immunopharmacology and Immunotoxicology Pub Date : 2025-04-01 Epub Date: 2025-01-29 DOI:10.1080/08923973.2025.2457971
Dewu Zhang, Ruiqi Li, Liping Liu, Ruijuan Lu, Juan Li, Yajing Hou
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Abstract

Objectives: Chitosan is widely used in medicine to regulate immune responses in T cells and dendritic cells. However, research on the regulation of mast cells (MCs) is scarce. Mas-related G-protein-coupled receptor X2 (MRGPRX2) is a key receptor that mediates MC activation. However, the inhibitory effects of chitosan on MRGPRX2 activation have not yet been reported. The aim of this study was to determine whether chitosan inhibits MRGPRX2-mediated MC activation and the molecular weight of chitosan with the best inhibitory effect.

Methods: Cytotoxic and activating effects of chitosan on LAD2 cells were evaluated in vitro. An in vitro MC degranulation reaction model and in vivo C48/80-induced local passive anaphylaxis mouse model were used to evaluate the inhibitory effect of chitosan on MRGPRX2 activation.

Key findings: Chitosan inhibited MC degranulation mediated by MRGPRX2 in vitro and reduced histamine, β-hexosaminidase, and cytokine release. Chitosan inhibited local pseudo-allergy and inflammatory mediator release by inhibiting MRGPRX2-mediated MC activation. Moreover, low-molecular-weight chitosan exhibited superior inhibitory activity against MRGPRX2.

Conclusions: Chitosan inhibited MRGPRX2-mediated MC degranulation in vivo and in vitro. Low molecular weight chitosan has the potential to be developed as a functional drug or food to assist in the treatment of MRGPRX2-regulated diseases.

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不同分子量壳聚糖对mrgprx2介导的肥大细胞脱颗粒及假过敏反应抑制作用的评价。
目的:壳聚糖在医学上广泛应用于调节T细胞和树突状细胞的免疫反应。然而,对肥大细胞(MCs)调控的研究却很少。mass相关g蛋白偶联受体X2 (MRGPRX2)是介导MC激活的关键受体。然而,壳聚糖对MRGPRX2激活的抑制作用尚未见报道。本研究的目的是确定壳聚糖是否抑制mrgprx2介导的MC活化,以及壳聚糖分子量的抑制效果最好。方法:体外观察壳聚糖对LAD2细胞的细胞毒和活化作用。采用体外MC脱粒反应模型和体内c48 /80诱导的局部被动过敏反应小鼠模型,评价壳聚糖对MRGPRX2激活的抑制作用。主要发现:壳聚糖抑制MRGPRX2介导的MC脱粒,减少组胺、β-己糖氨酸酶和细胞因子的释放。壳聚糖通过抑制mrgprx2介导的MC活化,抑制局部假性过敏和炎症介质的释放。低分子量壳聚糖对MRGPRX2具有较强的抑制活性。结论:壳聚糖对mrgprx2介导的MC脱粒具有体内外抑制作用。低分子量壳聚糖在mrgprx2调控疾病的治疗中,具有开发作为功能性药物或食品的潜力。
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来源期刊
CiteScore
5.40
自引率
0.00%
发文量
133
审稿时长
4-8 weeks
期刊介绍: The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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