Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice.

Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice.
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DOI:
10.1016/j.jaci.2013.06.008
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发表时间:
2013-10
期刊:
The Journal of allergy and clinical immunology
影响因子:
--
通讯作者:
Galli SJ
Galli SJ
中科院分区:
其他
文献类型:
--
作者:
Reber LL;Marichal T;Mukai K;Kita Y;Tokuoka SM;Roers A;Hartmann K;Karasuyama H;Nadeau KC;Tsai M;Galli SJ

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使用c-kit突变型肥大细胞(MC)缺陷小鼠和抗体介导的嗜碱性粒细胞耗竭的研究表明,MC和嗜碱性粒细胞都可能导致花生诱导的过敏反应(PIA)。然而,使用这种方法获得的数据的解释是复杂的,因为c-kit突变小鼠有几个表型异常,除了MC缺陷和嗜碱性粒细胞消耗抗体也可以与MC反应。我们分析:(1)选择性和诱导性去除MC或嗜碱性粒细胞后小鼠PIA特征的变化;(2)除MC和嗜碱性粒细胞外的效应细胞在PIA反应中的可能重要性。野生型(WT)和各种突变小鼠口服致敏花生提取物和霍乱毒素每周4周,并与花生提取物2周后腹腔内攻击。花生激发MC缺陷型KitW-sh/W-sh小鼠出现立即体温降低,以及通过抗体介导的中性粒细胞耗竭消除的体温晚期下降。白喉毒素介导的选择性消耗MC或嗜碱性粒细胞在Mcpt 5-Cre; iDTR和Mcpt 8DTR小鼠,分别,和治疗WT小鼠的嗜碱性粒细胞消耗抗体Ba 103,显着降低花生诱导的体温过低。非c-kit突变型MC-和嗜碱性粒细胞缺陷型Cpa 3-Cre; Mcl-1fl/fl小鼠对花生的反应降低,但仍显着。非c-kit突变小鼠中MC或嗜碱性粒细胞的诱导性和选择性消融可以显着减少PIA,但在几乎不存在这两种细胞类型的情况下仍然可以观察到对花生的部分反应。KitW-sh/W-sh小鼠中的嗜中性粒细胞可能影响这些小鼠在该PIA模型中的反应。
Studies using c-kit mutant mast cell (MC)-deficient mice and antibody-mediated depletion of basophils suggest that both MCs and basophils can contribute to peanut-induced anaphylaxis (PIA). However, interpretation of data obtained using such approaches is complicated because c-kit mutant mice have several phenotypic abnormalities in addition to MC deficiency and basophil-depleting antibodies can also react with MCs. We analyzed: (1) the changes in the features of PIA in mice after the selective and inducible ablation of MCs or basophils, and (2) the possible importance of effector cells other than MCs and basophils in the PIA response. Wild-type (WT) and various mutant mice were orally sensitized with peanut extract and cholera toxin weekly for 4 weeks and challenged intraperitoneally with peanut extract 2 weeks later. Peanut-challenged MC-deficient KitW-sh/W-sh mice developed reduced immediate hypothermia, as well as a late phase drop in body temperature that was abrogated by antibody-mediated depletion of neutrophils. Diphtheria toxin-mediated selective depletion of MCs or basophils in Mcpt5-Cre; iDTR and Mcpt8DTR mice, respectively, and treatment of WT mice with the basophil-depleting antibody Ba103, significantly reduced peanut-induced hypothermia. Non-c-kit mutant MC- and basophil-deficient Cpa3-Cre; Mcl-1fl/fl mice developed reduced, but still significant, responses to peanut. Inducible and selective ablation of MCs or basophils in non-c-kit mutant mice can significantly reduce PIA, but partial responses to peanut can still be observed in the virtual absence of both cell types. The neutrophilia in KitW-sh/W-sh mice may influence the responses of these mice in this PIA model.
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