Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling
Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling
复制标题
DOI：
10.1164/rccm.200308-1094oc
复制
发表时间：
2004-02-01
影响因子：
24.7
通讯作者：
Jordana, M
中科院分区：
文献类型：
--
作者：
Johnson, JR;Wiley, RE;Jordana, M
现在充分认识到哮喘是一种慢性性质的疾病，由间歇性或持续的空气过敏原暴露导致气道炎症。为了研究对连续抗原暴露的反应，小鼠鼻内暴露于屋尘螨提取物（HDM）或卵清蛋白连续5天，然后休息2天，连续7周。连续暴露于HDM，不像卵清蛋白，引起严重和持续的嗜酸性气道炎症。流式细胞术分析表明，肺中CD 4（+）淋巴细胞的积累，诱导型共刺激分子（T细胞活化的标志物）和T1/ST 2（辅助性T 2型效应细胞的标志物）的表达升高。我们还检测到增加和持续生产的辅助T细胞2型相关的细胞因子的HDM-Hisecl小鼠的脾细胞在体外HDM回忆。肺组织学分析显示暴露于HIDM的小鼠中存在气道重塑的证据，伴有杯状细胞增生、胶原沉积和收缩组织的支气管周围积聚。此外，HDM暴露小鼠表现出严重的气道高反应性乙酰甲胆碱。最后，在HDM暴露停止后长达9周研究这些反应。我们观察到，尽管气道炎症完全消退，但重塑变化并未消退，气道高反应性仅部分消退。
It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4(+) lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposecl mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HIDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly.