McKinley Laura, Kim Jiyoun, Bolgos Gerald L, Siddiqui Javed, Remick Daniel G
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Cytokine. 2005 Nov 3;32(3-4):178-85. doi: 10.1016/j.cyto.2005.09.006. Epub 2005 Nov 14.
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.
哮喘的病理生理学受到接触过敏原和内毒素的影响。尽管过敏原诱导的嗜酸性粒细胞增多的作用已得到广泛研究，但中性粒细胞介导的反应仍不清楚。中性粒细胞在哮喘反应中可能发挥作用，因为已证明人类中性粒细胞表达IgE受体以及许多与哮喘发病机制有关的细胞因子和趋化因子的受体。在本研究中，我们调查了中性粒细胞在一种新型的、屋尘提取物（HDE）诱导的类哮喘肺部炎症模型中的参与情况。用含有高水平蟑螂过敏原（377 U/ml Bla g1和6249 ng/ml Bla g2）的HDE对小鼠进行免疫和激发。用特异性兔抗血清抑制小鼠趋化因子KC和MIP-2的生物活性。对从支气管肺泡灌洗（BAL）液中回收的细胞进行差异计数显示，中和KC和MIP-2可显著减少中性粒细胞（减少86%）和淋巴细胞（减少76%）的肺部募集。中和这些趋化因子还产生了全身效应，血浆IgE水平显著降低，与对照血清处理的动物相比，为547 ng/ml±65，而对照血清处理的动物为1314 ng/ml±247。本研究表明，CXC趋化因子在过敏和哮喘中，在肺部细胞募集和全身免疫反应水平上均发挥重要作用。
