首页> 外文期刊>Life sciences >Leukotriene B4 is essential for selective eosinophil recruitment following allergen challenge of CD4+ cells in a model of chronic eosinophilic inflammation.
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Leukotriene B4 is essential for selective eosinophil recruitment following allergen challenge of CD4+ cells in a model of chronic eosinophilic inflammation.

机译:在慢性嗜酸性粒细胞炎症模型中,对CD4 +细胞进行变应原攻击后,白三烯B4对于选择性嗜酸性粒细胞募集至关重要。

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摘要

Subcutaneous heat-coagulated egg white implants (EWI) induce chronic, intense local eosinophilia in mice, followed by asthma-like responses to airway ovalbumin challenge. Our goal was to define the mechanisms of selective eosinophil accumulation in the EWI model. EWI carriers were challenged i.p. with ovalbumin and the contributions of cellular immunity and inflammatory mediators to the resulting leukocyte accumulation were defined through cell transfer and pharmacological inhibition protocols. Eosinophil recruitment required Major Histocompatibility Complex Class II expression, and was abolished by the leukotriene B4 (LTB4) receptor antagonist CP 105.696, the 5-lipoxygenase inhibitor BWA4C and the 5-lipoxygenase activating protein inhibitor MK886. Eosinophil recruitment in EWI carriers followed transfer of: a) CD4+ (but not CD4-) cells, harvested from EWI donors and restimulated ex vivo; b) their cell-free supernatants, containing LTB4. Restimulation in the presence of MK886 was ineffective. CC chemokine receptor ligand (CCL)5 and CCL2 were induced by ovalbumin challenge in vivo. mRNA for CCL17 and CCL11 was induced in ovalbumin-restimulated CD4+ cells ex vivo. MK886 blocked induction of CCL17. Pretreatment of EWI carriers with MK886 eliminated the effectiveness of exogenously administered CCL11, CCL2 and CCL5. In conclusion, chemokine-producing, ovalbumin-restimulated CD4+ cells initiate eosinophil recruitment which is strictly dependent on LTB4 production.
机译:皮下热凝卵清植入物(EWI)在小鼠中诱发慢性强烈的局部嗜酸性粒细胞增多,然后对气道卵清蛋白激发产生类似哮喘的反应。我们的目标是定义EWI模型中选择性嗜酸性粒细胞积累的机制。 EWI承运商在i.p.通过细胞转移和药理抑制方案确定卵清蛋白的含量,以及细胞免疫和炎性介质对白细胞积累的贡献。嗜酸性粒细胞的募集需要主要的组织相容性复合体II类表达,并且被白三烯B4(LTB4)受体拮抗剂CP 105.696、5-脂氧合酶抑制剂BWA4C和5-脂氧合酶活化蛋白抑制剂MK886废除了。在EWI携带者中嗜酸性粒细胞募集之后转移:a)从EWI供体收获并离体再刺激的CD4 +(但不是CD4-)细胞; b)他们的不含细胞的上清液,含有LTB4。在MK886存在下的再刺激无效。卵清蛋白攻击体内诱导CC趋化因子受体配体(CCL)5和CCL2。 CCL17和CCL11的mRNA在离体卵清蛋白重新刺激的CD4 +细胞中被诱导。 MK886阻止了CCL17的诱导。用MK886预处理EWI载体消除了外用CCL11,CCL2和CCL5的有效性。总之,产生趋化因子的卵清蛋白重新刺激的CD4 +细胞可引发嗜酸性粒细胞募集,而嗜酸性粒细胞募集严格依赖于LTB4的产生。

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