免疫后卵清蛋白激发豚鼠嗜酸性粒细胞募集而非支气管高反应性:时间进程及其与嗜酸性粒细胞激活状态的关系

Katharine H. Banner, William Paul, Clive P. Page
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引用次数: 16

摘要

嗜酸性粒细胞已知存在于过敏性哮喘患者的气道中,并被认为与伴随该疾病的病理生理变化有关,特别是对气道痉挛原的高反应性。然而,哮喘患者肺嗜酸性粒细胞积累与支气管高反应性之间的因果关系尚未得到证实。本研究在免疫豚鼠模型上研究了肺细胞内流的时间过程。嗜酸性粒细胞激活状态也与支气管对组胺的反应性一起测定。在Al(OH)3(0.5 ml) ip中致敏豚鼠[每只20 μg卵白蛋白(OVA)],然后在18-21天后用雾化的OVA (100 μg/ml)攻毒1 h。在OVA激发后的不同时间点(1 ~ 72小时),测量支气管对iv组胺的反应,并进行支气管肺泡灌洗(BAL)以评估肺细胞内流。测定BAL液上清中嗜酸性粒细胞过氧化物酶(EPO)和总蛋白水平。暴露于雾化OVA的致敏动物在24小时后嗜酸性粒细胞浸润显著增加(P<0.05与假免疫相比),并持续到72小时。尽管如此,在任何检查的时间点,OVA挑战都没有引起嗜酸性粒细胞激活(通过EPO释放测量)或支气管对组胺的高反应性。这些数据表明,致敏豚鼠的过敏原攻击可引起气道嗜酸性粒细胞积累,而不伴有气道高反应性或嗜酸性粒细胞激活。
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Ovalbumin Challenge Following Immunization Elicits Recruitment of Eosinophils but not Bronchial Hyperresponsiveness in Guinea-pigs: Time Course and Relationship to Eosinophil Activation Status

Eosinophils are known to be present in the airways of allergic asthmatics, and have been suggested to contribute to the pathophysiological changes accompanying this condition, particularly hyperresponsiveness to airway spasmogens. However, a causal relationship between pulmonary eosinophil accumulation and bronchial hyperresponsiveness in asthma is not proven. In the present study, the time course of pulmonary cell influx was investigated in an immunized guinea-pig model. Eosinophil activation status was also determined together with the bronchial responsiveness to histamine. Guinea-pigs were sensitized [20 μg ovalbumin (OVA) per animal in Al(OH)3(0.5 ml) ip] and subsequently challenged with aerosolized OVA (100 μg/ml) for 1 h 18–21 days later. At different time points (1 h to 72 h) after OVA challenge, bronchial responses to iv histamine were measured and bronchoalveolar lavage (BAL) was performed to assess pulmonary cell influx. Eosinophil peroxidase (EPO) and total protein levels were measured in BAL fluid supernatants. Exposure of sensitized animals to aerosolized OVA produced a significant increase (P<0.05 vs. sham immunized) in eosinophil infiltration 24 h later which was sustained up to 72 h. Despite this, OVA challenge did not cause either eosinophil activation, as measured by EPO release, or bronchial hyperresponsiveness to histamine at any of the time points examined. These data show that allergen challenge of sensitized guinea-pigs can elicit airway eosinophil accumulation without accompanying airways hyperresponsiveness or eosinophil activation.

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