CXC chemokines modulate IgE secretion and pulmonary inflammation in a model of allergic asthma
CXC chemokines modulate IgE secretion and pulmonary inflammation in a model of allergic asthma
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DOI：
10.1016/j.cyto.2005.09.006
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发表时间：
2005-11-03
期刊：
影响因子：
3.8
通讯作者：
Remick, DG
中科院分区：
文献类型：
--
作者：
McKinley, L;Kim, J;Remick, DG
哮喘的病理生理学受到暴露于过敏原和内毒素的影响。虽然过敏原诱导的嗜酸性粒细胞增多症的作用已被广泛研究，嗜酸性粒细胞介导的反应仍然难以捉摸。嗜中性粒细胞在哮喘反应中的作用是可能的，因为已经显示人嗜中性粒细胞表达IgE受体，以及与哮喘发病机制有关的许多细胞因子和趋化因子的受体。在这项研究中，我们研究了中性粒细胞参与一种新的，屋尘提取物（HDE）诱导的哮喘样肺部炎症模型。用含有高水平蟑螂过敏原的HDE（377 U/ml Bla g1和6249 ng/ml Bla g2）免疫小鼠并激发。小鼠趋化因子KC和MIP-2的生物学活性被特异性兔抗血清抑制。从支气管肺泡灌洗液（BAL）中回收的细胞的分类计数显示，KC和MIP-2的中和作用显著降低了中性粒细胞（减少86%）和淋巴细胞（减少76%）的肺募集。这些趋化因子的中和也发挥了全身效应，血浆IgE水平显著降低，547 ng/ml +/- 65，而对照血清处理动物的血浆IgE水平为1314 ng/ml +/- 247。这项研究表明，CXC趋化因子在肺细胞募集和全身免疫应答水平上在过敏和哮喘中起重要作用。(c)2005爱思唯尔有限公司保留所有权利。
The pathophysiology of asthma is influenced by exposure to allergens and endotoxin. Although the role of allergen-induced eosinophilia has been widely studied, neutrophil-mediated responses remain elusive. A role for neutrophils in the asthmatic responses is likely since human neutrophils have been shown to express IgE receptors, as well as receptors for many cytokines and chemokines implicated in the pathogenesis of asthma. In this study we investigated neutrophil involvement in a novel, house dust extract (HDE) induced model of asthma-like pulmonary inflammation. Mice were immunized and challenged with HDE containing high levels of cockroach allergens, 377 U/ml Bla g1 and 6249 ng/ml Bla g2. The biological activity of the murine chemokines KC and MIP-2 was inhibited with specific rabbit antisera. Differential counting of cells recovered from the bronchoalveolar lavage (BAL) fluid showed that neutralization of KC and MIP-2 significantly decreased pulmonary recruitment of neutrophils (reduced 86%) and lymphocytes (reduced 76%). Neutralization of these chemokines also exerted a systemic effect with a significant decrease in plasma IgE levels, 547 ng/ml +/- 65 compared to 1314 ng/ml +/- 247 for control sera treated animals. This study shows that CXC chemokines play an important role in allergy and asthma both at the level of pulmonary cell recruitment and systemic immune responses. (c) 2005 Elsevier Ltd. All rights reserved.