Granulocyte depletion and dexamethasone differentially modulate airways hyperreactivity, inflammation, mucus accumulation, and secretion induced by rmIL-13 or antigen
Granulocyte depletion and dexamethasone differentially modulate airways hyperreactivity, inflammation, mucus accumulation, and secretion induced by rmIL-13 or antigen
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DOI：
10.1165/ajrcmb.26.1.4618
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发表时间：
2002-01-01
影响因子：
6.4
通讯作者：
Vargaftig, BB
中科院分区：
文献类型：
--
作者：
Singer, M;Lefort, J;Vargaftig, BB
对高反应性BP2小鼠气管内给予白细胞介素(IL)-13可诱导支气管肺高反应性（BHR）、嗜酸性粒细胞增多、粘液和MUC5AC积累，与小鼠免疫后卵清蛋白（Ova）处理后观察到的情况相似（1,2）。IL-4 mrna在卵清蛋白（Ova）攻击后6小时达到峰值，然后下降，而IL-13的表达在较长时间内保持稳定，提示不同的作用。免疫小鼠卵后72 ~ 96 h吸入雾化的甲胆碱可降低上皮黏液含量，并使支气管肺泡灌洗液（BALF）黏液富集。使用长春碱或抗粒细胞抗体RB6-8C5研究粒细胞在粘液积聚中的作用，它们仅在有限程度上干扰过敏原诱导的粘液积聚。相比之下，嗜酸性粒细胞和嗜中性粒细胞炎症以及BHR完全被抑制。因此，粒细胞参与卵细胞诱导的BHR，而粘液积聚与BHR无关。粒细胞似乎与rmil -13诱导的黏液有更多的关系，抗粒细胞抗体会减少黏液，而BHR则不受影响。糖皮质激素地塞米松降低了卵子或rmIL-13后评估的所有参数。由于IL-13的作用是糖皮质激素敏感的，它们可能涉及次要机制。
The intratracheal administration of interleukin (IL)-13 to hyperresponsive BP2 mice induces bronchopulmonary hyperreactivity (BHR), eosinophilia, mucus and MUC5AC accumulation, similar to those observed after ovalbumin (Ova) treatment when mice are immunized (1, 2). mRNAs for IL-4 peaked at 6 h after Ova challenge, then vaned, whereas IL-13 expression was stable for a longer period, suggesting different effects. Inhalation of aerosolized methacholine by immunized mice 72-96 h after Ova reduced epithelial mucus content, and enriched the bronchoalveolar lavage fluid (BALF) mucus. The role of granulocytes for mucus accumulation was studied using vinblastine or the antigranulocyte antibody RB6-8C5, which interfered to a limited extent only with allergen-induced mucus accumulation. By contrast, eosinophilic and neutrophilic inflammation, as well as BHR, were completely suppressed. Granulocytes are thus involved in Ova-induced BHR, whereas mucus accumulation and BHR are unrelated. Granulocytes seem to be more implicated in rmIL-13-induced mucus, which is reduced by the antigranulocyte antibody, whereas BHR is unaffected. The glucocorticosteroid dexamethasone reduced all the parameters evaluated after Ova or after rmIL-13. Because the effects of IL-13 are glucocorticoid-sensitive, they probably involve secondary mechanisms.