Conditional neutrophil depletion challenges their contribution to mouse models of anaphylaxis.
Conditional neutrophil depletion challenges their contribution to mouse models of anaphylaxis.
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条件性中性粒细胞耗竭挑战了它们对小鼠过敏反应模型的贡献。
DOI：
10.1111/all.15738
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发表时间：
2023
期刊：
影响因子：
12.4
通讯作者：
Jönsson,Friederike
中科院分区：
文献类型：
--
作者：
Stackowicz,Julien;Gillis,CaitlinM;Godon,Ophélie;Iannascoli,Bruno;Conde,Eva;Leveque,Edouard;Worrall,WilliamPM;Galli,StephenJ;Bruhns,Pierre;Reber,LaurentL;Jönsson,Friederike
对编辑来说，过敏反应是一种急性的、具有潜在致命性的全身性过敏反应。在人类中，人们普遍认为过敏反应主要依赖于IgE抗体。1然而，免疫球蛋白也可能与输注药物引起的过敏反应有关。1已经建立了几种小鼠模型来识别过敏反应的关键效应细胞和介体。因此，在小鼠中已经确定了两种主要途径：一种是由Ig E、FcεRI、组胺和肥大细胞组成的“经典”途径，另一种是包括Ig G、FcγRIII、血小板激活因子以及--取决于所研究的过敏反应模型--巨噬细胞、嗜碱性粒细胞和/或中性粒细胞的“替代”途径。1-3我们和其他人基于使用去中性粒细胞单抗的实验，报道了中性粒细胞是小鼠免疫球蛋白过敏反应的潜在重要驱动因素。1、4相比之下，海峡等人。3表明抗原攻击前2天注射抗Gr-1单抗不能抑制免疫球蛋白G介导的过敏反应，提示这些单抗的作用可能与剂量、注射时机和所用模型有关。我们最近描述了一种依赖于中性粒细胞上白喉毒素(DT)受体选择性表达的可诱导的、抗体非依赖性的中性粒细胞耗竭小鼠模型(PMNDTR小鼠)。5在PMNDTR小鼠体内注射DT后，血液、脾和骨髓中性粒细胞明显减少(图S1a-D)。5因此，我们使用PMNDTR小鼠来重新评估中性粒细胞在过敏反应模型中的作用。为了诱导主动的全身过敏反应(ASA)，用弗氏佐剂乳化的BSA免疫小鼠，并用BSA攻击静脉注射BSA(图1A)，这是一种主要依赖免疫球蛋白的模型。4如预期的那样，在该模型中，用抗Ly6G或抗Gr-1去中性粒细胞单抗处理小鼠可显著降低体温和死亡率(图1B，C)。然而，引人注目的是，DT治疗的中性粒细胞缺乏的PMNDTR小鼠表现出与中性粒细胞充足的对照组相似的过敏反应严重程度(图1D，E)。我们在IgG2a或IgG2b诱导的被动全身过敏反应(PSA)模型中得到了类似的结果(图1F-J)。
To the Editor, Anaphylaxis is an acute and potentially lethal systemic allergic reaction. In humans, it is largely accepted that anaphylaxis relies predominately on IgE antibodies. 1 However, IgG might also contribute to anaphylaxis induced by infused drugs. 1 Several mouse models have been developed to identify key effector cells and mediators of anaphylaxis. Consequently, two main pathways have been identified in mice: a “classical” pathway consisting of IgE, FcεRI, histamine, and mast cells, and an “alternative” pathway involving IgG, FcγRIII, platelet-activating factor (PAF), and—depending on the anaphylaxis model studied—macrophages, basophils, and/or neutrophils. 1–3 We and others have reported that neutrophils are potentially important drivers of IgG anaphylaxis in mice, based on experiments using neutrophil-depleting mAbs. 1, 4 In contrast, Strait et al. 3 showed that injection of anti-Gr-1 mAb 2 days before antigen challenge failed to suppress IgG-mediated anaphylaxis, indicating that the effect of these mAbs likely depends on the dose, timing of injection, and specific model used. We recently described an inducible, antibody-independent, neutrophil depletion mouse model (PMNDTR mice), relying on the selective expression of the diphtheria toxin (DT) receptor on neutrophils. 5 Injection of DT in PMNDTR mice leads to a marked depletion of blood, spleen, and bone marrow neutrophils (Figure S1A–D). 5 We therefore used PMNDTR mice to reevaluate the contribution of neutrophils to anaphylaxis models. To elicit active systemic anaphylaxis (ASA), mice were immunized with BSA emulsified in Freund's adjuvant, and challenged iv with BSA (Figure 1A), a model that mostly relies on IgG. 4 As expected, pretreatment of mice with anti-Ly6G or anti-Gr-1 neutrophil-depleting mAbs markedly reduced hypothermia and mortality in this model (Figure 1B, C). Strikingly, however, DT-treated neutrophil-deficient PMNDTR mice exhibited similar anaphylaxis severity to neutrophilsufficient controls (Figure 1D, E). We obtained similar results in models of IgG2a-or IgG2b-induced passive systemic anaphylaxis (PSA)(Figure 1F–J).