Enhanced pulmonary allergic responses to Aspergillus in CCR2-/- mice
Enhanced pulmonary allergic responses to Aspergillus in CCR2-/- mice
复制标题
DOI：
10.4049/jimmunol.165.5.2603
复制
发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Hogaboam, CM
中科院分区：
文献类型：
--
作者：
Blease, K;Mehrad, B;Hogaboam, CM
对曲霉属的过敏反应会加重哮喘和囊性纤维化。针对烟曲霉活孢子或分生孢子的天然防御依赖于单核细胞和多形核白细胞的募集和激活，这些过程依赖于趋化性细胞因子。在本研究中，我们探讨了单核细胞趋化蛋白 - 1受体CCR2在肺部对烟曲霉分生孢子反应中的相对作用。在对可溶性烟曲霉抗原致敏后，由于靶向缺失而缺乏CCR2的小鼠与表达CCR2的小鼠（即CCR2(+/+)小鼠）相比，对活分生孢子的肺内激发的损伤作用明显更敏感。CCR2(-/-)小鼠在多形核细胞募集方面存在重大缺陷，但这些小鼠的支气管肺泡灌洗液样本中嗜酸性粒细胞和淋巴细胞也明显更多。与CCR2(+/+)小鼠相比，CCR2(-/-)小鼠的血清总IgE水平以及全肺的IL - 5、IL - 13、嗜酸性粒细胞趋化因子和RANTES水平也显著升高。在分生孢子激发后，与CCR2(+/+)小鼠相比，CCR2(-/-)小鼠的气道炎症、对痉挛原的高反应性以及上皮下纤维化明显增强。因此，这些研究结果表明，CCR2在针对烟曲霉的免疫反应中起重要作用，从而限制了对这种真菌的过敏性气道炎症和重塑反应。
Allergic responses to Aspergillus species exacerbate asthma and cystic fibrosis, The natural defense against live Aspergillus fumigatus spores or conidia depends on the recruitment and activation of mononuclear and polymorphonuclear leukocytes, events that are dependent on chemotactic cytokines, in this study, we explored the relative contribution of the monocyte chemoattractant protein-1 receptor, CCR2, in the pulmonary response to A, fumigatus conidia, Following sensitization to soluble A, fumigatus Ags, mire larking CCR2 due to targeted deletion were markedly more susceptible to the injurious effects of an intrapulmonary challenge with live conidia compared with mice that expressed CCR2 or CCR2(+/+). CCR2(-/-) mice exhibited a major defect in the recruitment of polymorphonuclear cells, but these mice also had significantly more eosinophils and lymphocytes in bronchoalveolar lavage samples. CCR2(-/)- mice also had significant increases in serum levels of total IgE and whole lung levels of IL-5, IL-13, eotaxin, and RANTES compared with CCR2(+/+) mice, Airway inflammation, hyper-responsiveness to spasmogens, and subepithelial fibrosis were significantly enhanced in CCR2(-/-) mice compared with CCR2(+/+) mice after the conidia challenge. Thus, these findings demonstrate that CCR2 plays an important role in the immune response against A. fumigatus, thereby limiting the allergic airway inflammatory and remodeling responses to this fungus.