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首页> 外文期刊>Journal of Allergy >Neutrophil Inhibitory Factor Selectively Inhibits the Endothelium-Driven Transmigration of Eosinophils In Vitro and Airway Eosinophilia in OVA-Induced Allergic Lung Inflammation
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Neutrophil Inhibitory Factor Selectively Inhibits the Endothelium-Driven Transmigration of Eosinophils In Vitro and Airway Eosinophilia in OVA-Induced Allergic Lung Inflammation

机译：中性粒细胞抑制因子在OVA引起的过敏性肺炎症中选择性抑制嗜酸性粒细胞的内皮驱动迁移和气道嗜酸性粒细胞的迁移。

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Leukocyte adhesion molecules are involved in cell recruitment in an allergic airway response and therefore provide a target for pharmaceutical intervention. Neutrophil inhibitory factor (NIF), derived from canine hookworm (Ancylostoma caninum), binds selectively and competes with the A-domain of CD11b for binding to ICAM-1. The effect of recombinant NIF was investigated. Intranasal administration of rNIF reduced pulmonary eosinophilic infiltration, goblet cell hyperplasia, and Th2 cytokine production in OVA-sensitized mice. In vitro, transendothelial migration of human blood eosinophils across IL-4-activated umbilical vein endothelial cell (HUVEC) monolayers was inhibited by rNIF (IC50  nM; mean ± SEM), but not across TNF or IL-1-activated HUVEC monolayers. Treatment of eosinophils with rNIF together with mAb 60.1 directed against CD11b or mAb 107 directed against the metal ion-dependent adhesion site (MIDAS) of the CD11b A-domain resulted in no further inhibition of transendothelial migration suggesting shared functional epitopes. In contrast, rNIF increased the inhibitory effect of blocking mAbs against CD18, CD11a, and VLA-4. Together, we show that rNIF, a selective antagonist of the A-domain of CD11b, has a prominent inhibitory effect on eosinophil transendothelial migration in vitro, which is congruent to the in vivo inhibition of OVA-induced allergic lung inflammation.
机译：白细胞粘附分子在过敏性气道反应中参与细胞募集，因此为药物干预提供了靶标。中性粒细胞抑制因子（NIF），源于犬钩虫（Ancylostoma caninum），选择性结合并与CD11b的A结构域竞争与ICAM-1的结合。研究了重组NIF的作用。鼻内给药rNIF可减少OVA致敏小鼠的肺嗜酸性粒细胞浸润，杯状细胞增生和Th2细胞因子的产生。在体外，rNIF（IC50 nM;平均值±SEM）抑制人血嗜酸性粒细胞跨IL-4激活的脐静脉内皮细胞（HUVEC）单层的内皮迁移，但不跨TNF或IL-1激活的HUVEC单层。用rNIF与针对CD11b的mAb 60.1或针对CD11b A结构域的金属离子依赖性粘附位点（MIDAS）的mAb 107一起治疗嗜酸性粒细胞不会进一步抑制跨内皮迁移，提示存在共有的功能性表位。相反，rNIF增加了阻断mAb对CD18，CD11a和VLA-4的抑制作用。在一起，我们表明，rNIF，CD11b的A结构域的选择性拮抗剂，对体外嗜酸性粒细胞跨内皮迁移具有显着的抑制作用，这与OVA诱导的过敏性肺部炎症的体内抑制作用一致。

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