Antigen sensitization modulates alveolar macrophage functions in an asthma model
Antigen sensitization modulates alveolar macrophage functions in an asthma model
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DOI：
10.1152/ajplung.00219.2005
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Bissonnette, ÉY
中科院分区：
文献类型：
--
作者：
Careau, É;Proulx, LI;Bissonnette, ÉY
我们之前已经证明，从过敏抵抗大鼠到肺泡巨噬细胞缺失的过敏大鼠的肺泡巨噬细胞过继转移可以阻止气道高反应性的发展，这表明肺泡巨噬细胞在哮喘发病机制中起重要作用。鉴于卵清蛋白致敏可以调节肺泡巨噬细胞细胞因子的产生，我们研究了致敏和未致敏的肺泡巨噬细胞在哮喘模型中的作用。在致敏前24小时，将未致敏或致敏的褐挪威大鼠的肺泡巨噬细胞转移到致敏大鼠的肺泡巨噬细胞缺失。第二天测量气道对甲胆碱的反应性和气道炎症。肺泡巨噬细胞缺失致敏大鼠接受未致敏肺泡巨噬细胞后，肺阻力增加200%所需的甲胆碱浓度明显高于接受致敏肺泡巨噬细胞的肺泡巨噬细胞缺失致敏大鼠。致敏大鼠接受未致敏肺泡巨噬细胞的支气管肺泡灌洗液中肿瘤坏死因子水平明显低于接受致敏肺泡巨噬细胞的大鼠。有趣的是，与致敏大鼠相比，未致敏动物的肺泡巨噬细胞表现出更高的吞噬活性，表明致敏调节了肺泡巨噬细胞的吞噬功能。我们的数据表明过敏原致敏对肺泡巨噬细胞功能在哮喘发病中的重要作用。
We have previously demonstrated that adoptive transfer of alveolar macrophages from allergy-resistant rats to alveolar macrophage-depleted allergic rats prevents airway hyperresponsiveness development, suggesting an important role for alveolar macrophages in asthma pathogenesis. Given that ovalbumin sensitization can modulate alveolar macrophage cytokine production, we investigated the role of sensitized and unsensitized alveolar macrophages in an asthma model. Alveolar macrophages from unsensitized or sensitized Brown Norway rats were transferred to alveolar macrophage-depleted sensitized rats 24 h before allergen challenge. Airway responsiveness to methacholine and airway inflammation were measured the following day. Methacholine concentration needed to increase lung resistance by 200% was significantly higher in alveolar macrophage-depleted sensitized rats that received unsensitized alveolar macrophages compared with alveolar macrophage-depleted sensitized rats that received sensitized alveolar macrophages. Tumor necrosis factor levels in bronchoalveolar lavage fluid of sensitized rats that received unsensitized alveolar macrophages were significantly lower compared with rats that received sensitized alveolar macrophages. Interestingly, alveolar macrophages of unsensitized animals showed higher phagocytosis activity compared with alveolar macrophages of sensitized rats, suggesting that sensitization modulates alveolar macrophage phagocytosis function. Our data suggest an important role of allergen sensitization on alveolar macrophage function in asthma pathogenesis.