Pathways of anaphylaxis in the mouse
Pathways of anaphylaxis in the mouse
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DOI：
10.1067/mai.2002.123302
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发表时间：
2002-04-01
影响因子：
14.2
通讯作者：
Finkelman, FD
中科院分区：
文献类型：
--
作者：
Strait, RT;Morris, SC;Finkelman, FD
背景资料：尽管过敏反应典型地由IgE、FcepsilonRI、肥大细胞和组胺介导，但几项啮齿动物研究表明，涉及IgG、FcgammaRIII、巨噬细胞和血小板以及血小板活化因子（PAF）的替代途径可能在过敏反应中更重要抗原挑战。目标：我们试图确定在以肥大细胞增多症和高水平抗原-为特征的小鼠模型中，过敏反应的经典途径和替代途径的相对作用。方法：用山羊抗小鼠IgD抗体免疫野生型、IgE缺陷型、FeepsilonRI缺陷型和肥大细胞缺陷型小鼠，其诱导肥大细胞增多症和大的IgE和IgG抗山羊IgG应答，然后在14天后用抗原（山羊IgG）或大鼠抗小鼠IgE mAb攻击。特异性血管活性介质、细胞类型、IG同种型。或IG受体在一些实验中在攻击前被阻断或消除。过敏反应的严重程度通过体温的变化来衡量。结果：相同剂量的抗原或抗IgE mAb诱导相似的过敏反应。抗IgE单抗诱导的过敏反应主要由组胺介导，是Fc γ R Ⅲ和巨噬细胞依赖的，而肥大细胞和血小板对抗原诱导的过敏反应均不起作用，主要由PAF介导。巨噬细胞和RAF途径，即使在以强肥大细胞和IgE应答为特征的实验模型中也是如此。Fc γ RIII在人巨噬细胞上的存在使得IgG、Fc γ RIII、巨噬细胞和PAF途径也有助于人过敏反应成为可能。
Background: Although anaphylaxis is classically mediated by IgE, FcepsilonRI, mast cells, and histamine, several rodent studies suggest that an alternative pathway involving IgG, FcgammaRIII, macrophages and platelets, and platelet-activating factor (PAF) may be more important in the anaphylactic response to antigen challenge.Objectives: We sought to determine the relative roles of the classical and alternative pathways of anaphylaxis in a mouse model characterized by mastocytosis and a high level of antigen-specific IgE antibody.Methods: Wild-type, IgE-deficient, FeepsilonRI-deficient, and mast cell-deficient mice were immunized with goat anti-mouse IgD antibody, which induces mastocytosis and a large IgE and IgG anti-goat IgG response, and then challenged 14 days later with antigen (goat IgG) or rat anti-mouse IgE mAb. Specific vasoactive mediators, cell types, Ig isotypes. or Ig receptors were blocked or eliminated before challenge in some experiments. The severity of anaphylaxis was gauged by changes in body, temperature. physical activity, and mortality.Results: Equal doses of antigen or anti-IgE mAb induced similar anaphylactic responses. Anti-IgE mAb-induced anaphylaxis was FcepsilonRI and mast cell dependent and mediated predominantly by histamine, In contrast, neither mast cells nor platelets appeared important for antigen-induced anaphylaxis which was FcgammaRIII and macrophage dependent and mediated predominantly by PAF.Conclusions: Antigen-induced anaphylaxis in the mouse proceeds primarily through the IgG, FcgammaRIII. macrophage, and RAF pathway, even in an experimental model that is characterized by strong mast cell and IgE responses. The presence of FcgammaRIII on human macrophages makes it possible that the IgG, FcgammaRIII, macrophage, and PAF pathway also contributes to human anaphylaxis.