Prolonged allergen challenge in mice leads to persistent airway remodelling.
Prolonged allergen challenge in mice leads to persistent airway remodelling.
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DOI：
10.1111/j.1365-2222.2004.01895.x
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发表时间：
2004-03
期刊：
影响因子：
--
通讯作者：
Lloyd CM
中科院分区：
文献类型：
--
作者：
McMillan SJ;Lloyd CM
炎症浸润、气道高反应性、杯状细胞增生和上皮下增厚是慢性哮喘的特征。目前过敏原诱导的气道炎症的动物模型通常集中于过敏原暴露后的急性炎症，并且不能模拟所有这些特征。本研究的目的是使用小鼠模型的长期过敏原诱导的气道炎症，以表征细胞和分子参与随后的气道重塑。此外，我们研究了在没有持续的过敏原挑战的情况下，重塑是否持续存在。在致敏小鼠（急性期）中进行6次过敏原激发后，诱导急性肺嗜酸性粒细胞增多和气道高反应性。随后用卵清蛋白（OVA）（慢性期）每周攻击小鼠三次，直至第55天。为了研究病理学的持续性，将一组小鼠再放置4周而不进行进一步的过敏原攻击（第80天）。延长的OVA激发方案引起显著的气道重塑，这在急性期是不存在的。具体而言，重塑的特征在于胶原沉积以及气道平滑肌和杯状细胞增生。重要的是，这些气道变化以及组织嗜酸性粒细胞增多在没有进一步过敏原激发的情况下持续存在。细胞因子检测显示慢性期IL-4和肿瘤生长因子-β1显著上调。有趣的是，虽然IL-4水平在慢性期显著增加，但IL-13水平下降。Th 1相关细胞因子IFN-γ的水平也在慢性期增加。总之，我们已经证明，长期的过敏原挑战的结果在持续气道壁重塑。
Inflammatory infiltrates, airway hyper-responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen-induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features. The aim of this study was to use a murine model of prolonged allergen-induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge. Acute pulmonary eosinophilia and airways hyper-reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80). The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up-regulation of IL-4 and tumour growth factor-β1 during the chronic phase. Interestingly, while IL-4 levels were significantly increased during the chronic phase, levels of IL-13 fell. Levels of the Th1-associated cytokine IFN-γ also increased during the chronic phase. In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.
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白介素5缺乏消除小鼠哮喘模型中的嗜酸性粒细胞，气道高反应性和肺损伤。
影响因子：
15.3
作者：
Foster, PS;Hogan, SP;Ramsay, AJ;Matthaei, KI;Young, IG
通讯作者：
Young, IG
DOI：
10.1084/jem.194.6.809
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Homer RJ;Zhu Z;Lanone S;Wang X;Koteliansky V;Shipley JM;Gotwals P;Noble P;Chen Q;Senior RM;Elias JA
通讯作者：
Elias JA
DOI：
10.1165/ajrcmb.17.3.2733
发表时间：
1997-09-01
影响因子：
6.4
作者：
Minshall, EM;Leung, DYM;Hamid, Q
通讯作者：
Hamid, Q
DOI：
10.1164/ajrccm.156.3.9606031
发表时间：
1997-09-01
影响因子：
24.7
作者：
Hamelmann, E;Schwarze, J;Gelfand, EW
通讯作者：
Gelfand, EW
DOI：
10.1164/ajrccm/140.6.1745
发表时间：
1989-12-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
JEFFERY, PK;WARDLAW, AJ;KAY, AB
通讯作者：
KAY, AB