Mast cells mediate hyperoxia-induced airway hyper-reactivity in newborn rats.
Mast cells mediate hyperoxia-induced airway hyper-reactivity in newborn rats.
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DOI：
10.1203/pdr.0b013e3181e0cd97
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发表时间：
2010-07
影响因子：
3.6
通讯作者：
Auten RL
中科院分区：
文献类型：
--
作者：
Schultz ED;Potts EN;Mason SN;Foster WM;Auten RL
早产儿在氧化应激和炎症后发生气道高反应性的风险增加。肥大细胞部分通过介质释放促进气道高反应性，因此我们试图确定阻断肥大细胞脱颗粒或募集是否可以防止高氧诱导的气道高反应性、肥大细胞积聚和气道平滑肌变化。大鼠出生时暴露于空气或60%O2 14天，诱导显着增加的气道高反应性（AHR）在后一组，诱导雾化乙酰甲胆碱的挑战，通过强迫呼吸测量。与溶剂处理对照组相比，每天腹膜内注射克罗美因（出生后第1-14天）可预防高氧诱导的AHR，在出生后第5-14天用伊马替尼处理也是如此。色甘酸可以防止气管中肥大细胞的脱颗粒，但不能防止肺门气道中肥大细胞的脱颗粒，并阻止肺门气道中肥大细胞的积聚。伊马替尼治疗完全阻断了气管/肺门气道组织中肥大细胞的积聚。新生大鼠高氧诱导的AHR至少部分通过肥大细胞介导。
Premature infants are at increased risk of developing airway hyper-reactivity following oxidative stress and inflammation. Mast cells contribute to airway hyper-reactivity partly by mediator release, so we sought to determine if blocking mast cell degranulation or recruitment prevents hyperoxia-induced airway hyper-reactivity, mast cell accumulation, and airway smooth muscle changes. Rats were exposed at birth to air or 60% O2 for 14 days, inducing significantly increased airway hyper-reactivity (AHR) in the latter group, induced by nebulized methacholine challenge, measured by forced oscillometry. Daily treatment (postnatal days 1-14) with intraperitoneal cromolyn prevented hyperoxia-induced AHR, as did treatment with imatinib on postnatal days 5-14, compared with vehicle treated controls. Cromolyn prevented mast cell degranulation in the trachea but not hilar airways, and blocked mast cell accumulation in the hilar airways. Imatinib treatment completely blocked mast cell accumulation in tracheal/hilar airway tissues. Hyperoxia-induced AHR in neonatal rats is mediated, at least in part, via the mast cell.