Antibody-antigen interaction in the airway drives early granulocyte recruitment through BLT1
Antibody-antigen interaction in the airway drives early granulocyte recruitment through BLT1
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DOI：
10.1152/ajplung.00212.2005
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发表时间：
2006-01-01
影响因子：
4.9
通讯作者：
Luster, AD
中科院分区：
文献类型：
--
作者：
Medoff, BD;Tager, AM;Luster, AD
哮喘急性发作时，呼吸道抗体与抗原的相互作用会引发炎症反应。这种炎症反应的特点是粒细胞重新聚集到呼吸道。在哮喘小鼠模型中，粒细胞重新聚集到肺中有助于气道高反应性(AHR)、粘液产生和气道重塑的发展。白三烯B-4是抗原刺激后释放的一种介质，通过其受体BLT1对粒细胞具有趋化活性。我们研究了BLT1在抗原攻击后粒细胞募集中的作用。用卵白蛋白(OVA)致敏和激发野生型小鼠和BLT1(-/-)小鼠，诱导急性过敏性呼吸道炎症。此外，为了探索抗体-抗原相互作用的相关性，我们将与抗OVA 1GG(1)或抗OVA IgE结合的OVA注射到幼小野生型和BLT1(-/-)小鼠的气管内。测定肺细胞成分、细胞因子水平、组织学和AHR。经卵清蛋白致敏和攻击后，BLT1(-/-)小鼠的中性粒细胞和嗜酸性粒细胞在每日1-2次抗原攻击后，其呼吸道中性粒细胞和嗜酸性粒细胞的募集率与野生型动物相比显著减少，但在每天3-4次抗原攻击后，这一差异不明显。粘液产量和AHR未受影响。气管内注射结合1gG1或IgE的OVA可使野生型小鼠的中性粒细胞重新聚集到呼吸道，但对BLT1(-/-)小鼠无此作用。我们得出结论，在急性哮喘的小鼠模型中，BLT1在抗原-抗体相互作用的反应中介导粒细胞早期募集到呼吸道。
Antibodyantigen interactions in the airway initiate inflammation in acute asthma exacerbations. This inflammatory response is characterized by the recruitment of granulocytes into the airways. In murine models of asthma, granulocyte recruitment into the lung contributes to the development of airway hyperresponsiveness (AHR), mucus production, and airway remodeling. Leukotriene B-4 is a mediator released following antigen challenge that has chemotactic activity for granulocytes, mediated through its receptor, BLT1. We investigated the role of BLT1 in granulocyte recruitment following antigen challenge. Wild- type mice and BLT1(-/-) mice were sensitized and challenged with ovalbumin (OVA) to induce acute allergic airway inflammation. In addition, to explore the relevance to antibody-antigen interactions, we injected OVA bound to anti-OVA 1gG(1) or anti-OVA IgE intratracheally into naive wild-type and BLT1(-/-) mice. Cell composition of the lungs, cytokine levels, histology, and AHR were determined. After sensitization and challenge with ovalbumin, there was significantly reduced neutrophil and eosinophil recruitment into the airways of BLT1(-/-) mice compared with wild-type animals after one or two daily antigen challenges, but this difference was not seen after three or four daily antigen challenges. Mucus production and AHR were not affected. Intratracheal injection of OVA bound to 1gG1 or IgE induced neutrophil recruitment into the airways in wild-type mice but not in the BLT1(-/-) mice. We conclude that BLT1 mediates early recruitment of granulocytes into the airway in response to antigen-antibody interactions in a murine model of acute asthma.