Quaternary ammoniums activate human dendritic cells and induce a specific T-cell response in vitro.

IF 6.2 2区 医学 Q1 ALLERGY Allergology International Pub Date : 2024-09-04 DOI:10.1016/j.alit.2024.07.003
Marine Peyneau, Mathilde Zeller, Virginie Paulet, Benoît Noël, Marie-Hélène Damiens, Natacha Szely, Andreas Natsch, Marc Pallardy, Sylvie Chollet-Martin, Luc de Chaisemartin, Saadia Kerdine-Römer
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Abstract

Background: In many countries, neuro-muscular blocking agents (NMBAs) are the first cause of perioperative anaphylaxis. Epidemiological studies identified pholcodine, a quaternary ammonium-containing opiate as one of the sensitization sources. However, NMBA anaphylaxis exists in countries where pholcodine was unavailable, prompting the hypothesis of other sensitizing molecules, most likely quaternary ammonium compounds (QACs). Indeed, QACs are commonly used as disinfectants, antiseptics, preservatives, and detergents. Occupational exposure to QACs has been reported as a risk factor for NMBA anaphylaxis, but little is known about the sensitization mechanism and the capacity of these molecules to elicit an immune response. We aimed to establish the immunogenicity of QACs representative of the main existing chemical structures.

Methods: We measured the sensitization potential of seven QACs (two polyquaterniums, three alkyl-ammoniums and two aromatic ammoniums) by using two standard dendritic cells (DCs) models (THP-1 cell line and monocyte derived-dendritic cells). The allergenicity of the sensitizing compounds was further tested in heterologous and autologous T-cell-DC co-culture models.

Results: Amongst the seven molecules tested, four could modulate activation markers on DCs, and thus can be classified as chemical sensitizers (polyquaterniums-7 and -10, ethylhexadecyldimethylammonium and benzethonium). This activation was accompanied by the secretion of pro-inflammatory and maturation cytokines. Furthermore, activation by polyquaternium-7 could induce T-cell proliferation in heterologous and autologous coculture models, demonstrating that this molecule can induce a specific CD4+ T cell response.

Conclusions: We provide evidence at the cellular level that some QACs can elicit an immune response, which could be in line with the hypothesis of these molecules' role in NMBA sensitization.

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季铵盐在体外激活人类树突状细胞并诱导特异性 T 细胞反应。
背景:在许多国家,神经肌肉阻断剂(NMBA)是导致围手术期过敏性休克的首要原因。流行病学研究发现,含有季铵的阿片类药物芬可待因是致敏源之一。然而,在无法获得酚可定的国家也存在 NMBA 过敏性休克,这促使人们提出了其他致敏分子的假设,最有可能是季铵化合物(QAC)。事实上,QACs 常用作消毒剂、防腐剂、防腐剂和洗涤剂。据报道,职业性接触 QACs 是导致 NMBA 过敏性休克的一个危险因素,但人们对这些分子的致敏机制和引起免疫反应的能力知之甚少。我们的目的是确定代表现有主要化学结构的 QAC 的免疫原性:我们使用两种标准树突状细胞(DCs)模型(THP-1 细胞系和单核细胞衍生树突状细胞)测量了七种 QACs(两种聚季铵盐、三种烷基铵和两种芳香族铵)的致敏潜力。在异源和自源 T 细胞-DC 共培养模型中进一步测试了致敏化合物的过敏性:结果:在测试的七种分子中,有四种能调节 DC 的活化标记,因此可归类为化学致敏剂(聚季铵盐-7 和-10、乙基十六烷基二甲基铵和苄基铵)。这种激活伴随着促炎细胞因子和成熟细胞因子的分泌。此外,在异源和自体共培养模型中,聚季铵盐-7 的活化可诱导 T 细胞增殖,这表明该分子可诱导特定的 CD4+ T 细胞反应:我们在细胞水平上提供了一些 QACs 可以引起免疫反应的证据,这可能与这些分子在 NMBA 致敏中发挥作用的假设相符。
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来源期刊
Allergology International
Allergology International ALLERGY-IMMUNOLOGY
CiteScore
12.60
自引率
5.90%
发文量
96
审稿时长
29 weeks
期刊介绍: Allergology International is the official journal of the Japanese Society of Allergology and publishes original papers dealing with the etiology, diagnosis and treatment of allergic and related diseases. Papers may include the study of methods of controlling allergic reactions, human and animal models of hypersensitivity and other aspects of basic and applied clinical allergy in its broadest sense. The Journal aims to encourage the international exchange of results and encourages authors from all countries to submit papers in the following three categories: Original Articles, Review Articles, and Letters to the Editor.
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