Plopper Charles G, Smiley-Jewell Suzette M, Miller Lisa A, Fanucchi Michelle V, Evans Michael J, Buckpitt Alan R, Avdalovic Mark, Gershwin Laurel J, Joad Jesse P, Kajekar Radhika, Larson Shawnessy, Pinkerton Kent E, Van Winkle Laura S, Schelegle Edward S, Pieczarka Emily M, Wu Reen, Hyde Dalla M
Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA.
Toxicol Pathol. 2007 Jan;35(1):97-110. doi: 10.1080/01926230601132030.
The recent, dramatic increase in the incidence of childhood asthma suggests a role for environmental contaminants in the promotion of interactions between allergens and the respiratory system of young children. To establish whether exposure to an environmental stressor, ozone (O3), and an allergen, house dust mite (HDMA), during early childhood promotes remodeling of the epithelial-mesenchymal trophic unit (EMTU) of the tracheobronchial airway wall by altering postnatal development, infant rhesus monkeys were exposed to cyclic episodes of filtered air (FA), HDMA, O3, or HDMA plus O3. The following alterations in the EMTU were found after exposure to HDMA, O3, or HDMA plus O3: (1) reduced airway number; (2) hyperplasia of bronchial epithelium; (3) increased mucous cells; (4) shifts in distal airway smooth muscle bundle orientation and abundance to favor hyperreactivity; (5) interrupted postnatal basement membrane zone differentiation; (6) modified epithelial nerve fiber distribution; and (7) reorganization of the airway vascular and immune system.
cyclic challenge of infants to toxic stress during postnatal lung development modifies the EMTU. This exacerbates the allergen response to favor development of intermittent airway obstruction associated with wheeze. And, exposure of infants during early postnatal lung development initiates compromises in airway growth and development that persist or worsen as growth continues, even with cessation of exposure.
近期儿童哮喘发病率急剧上升，这表明环境污染物在促进过敏原与幼儿呼吸系统相互作用中发挥了作用。为确定幼儿期暴露于环境应激源臭氧（O3）和过敏原屋尘螨（HDMA）是否通过改变出生后发育促进气管支气管气道壁上皮-间充质营养单位（EMTU）的重塑，将幼年恒河猴暴露于过滤空气（FA）、HDMA、O3或HDMA加O3的循环发作中。在暴露于HDMA、O3或HDMA加O3后，发现EMTU有以下改变：（1）气道数量减少；（2）支气管上皮增生；（3）黏液细胞增加；（4）远端气道平滑肌束方向和丰度改变，有利于高反应性；（5）出生后基底膜区分化中断；（6）上皮神经纤维分布改变；（7）气道血管和免疫系统重组。
出生后肺部发育期间婴儿反复受到毒性应激会改变EMTU。这会加剧过敏原反应，有利于与喘息相关的间歇性气道阻塞的发展。而且，出生后早期肺部发育期间婴儿的暴露会引发气道生长和发育的损害，即使停止暴露，随着生长继续，这些损害仍会持续或恶化。
