Ablation of eosinophils leads to a reduction of allergen-induced pulmonary pathology
Ablation of eosinophils leads to a reduction of allergen-induced pulmonary pathology
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DOI：
10.1152/ajplung.00260.2002
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发表时间：
2003-01-01
影响因子：
4.9
通讯作者：
Lee, JJ
中科院分区：
文献类型：
--
作者：
Justice, JP;Borchers, MT;Lee, JJ
研究了一种利用抗体介导的清除方法，从卵清蛋白（OVA）致敏/激发小鼠的肺中清除嗜酸性粒细胞。同时给予大鼠抗小鼠CCR3单克隆抗体[即腹腔（全身）和肺（局部）气雾剂]，可导致肺中嗜酸性粒细胞的消除，从而使气道管腔基本上缺乏嗜酸性粒细胞。此外，血管周围/支气管周围嗜酸性粒细胞数量减少到与盐胁迫动物难以区分的水平。这种抗体介导的消耗不伴有对任何其他白细胞群的影响，包括但不限于T细胞和肥大细胞/嗜碱性粒细胞。此外，ova处理小鼠的其他潜在过敏性炎症反应未见影响，包括ova特异性免疫球蛋白的产生以及T细胞依赖性Th2细胞因子的细化。在ova处理的小鼠中，几乎所有肺嗜酸性粒细胞的消融（即不同时影响T细胞活性）导致黏液积聚显著减少，并消除了过敏原诱导的气道高反应性。这些数据表明过敏原介导的肺部病变与嗜酸性粒细胞之间存在直接的因果关系。
A strategy to deplete eosinophils from the lungs of ovalbumin (OVA)-sensitized/ challenged mice was developed using antibody-mediated depletion. Concurrent administration [viz. the peritoneal cavity (systemic) and as an aerosol to the lung (local)] of a rat anti-mouse CCR3 monoclonal antibody resulted in the abolition of eosinophils from the lung such that the airway lumen was essentially devoid of eosinophils. Moreover, perivascular/peribronchial eosinophil numbers were reduced to levels indistinguishable from saline-challenged animals. This antibody-mediated depletion was not accompanied by effects on any other leukocyte population, including, but not limited to, T cells and mast cells/basophils. In addition, no effects were observed on other underlying allergic inflammatory responses in OVA-treated mice, including OVA-specific immunoglobulin production as well as T cell-dependent elaboration of Th2 cytokines. The ablation of virtually all pulmonary eosinophils in OVA-treated mice (i.e., without concurrent effects on T cell activities) resulted in a significant decrease in mucus accumulation and abolished allergen-induced airway hyperresponsiveness. These data demonstrate a direct causative relationship between allergen-mediated pulmonary pathologies and eosinophils.