Abstract
Premature infants are at increased risk of developing airway hyper-reactivity (AHR) after oxidative stress and inflammation. Mast cells contribute to AHR partly by mediator release, so we sought to determine whether blocking mast cell degranulation or recruitment prevents hyperoxia-induced AHR, mast cell accumulation, and airway smooth muscle (ASM) changes. Rats were exposed at birth to air or 60% O2 for 14 d, inducing significantly increased AHR in the latter group, induced by nebulized methacholine challenge and measured by forced oscillometry. Daily treatment (postnatal d 1–14) with intraperitoneal cromolyn prevented hyperoxia-induced AHR, as did treatment with imatinib on postnatal d 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.
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Abbreviations
- AHR:
-
airway hyper-reactivity
- ASM:
-
airway smooth muscle
- RMCP:
-
rat mast cell proteases
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Acknowledgements
We thank Mary Whorton for the technical assistance. We also thank Drs. David Tanaka, Mary Sunday, and Ronald Goldberg for the helpful discussions.
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Supported by Children's Miracle Network, grant HD-043728 from the National Institutes of Child Health and Human Development, grant HL-067021 from the National Heart, Lung and Blood Institute, and grants ES-011961 and -012496 from the National Institute of Environmental Health Sciences.
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Schultz, E., Potts, E., Mason, S. et al. Mast Cells Mediate Hyperoxia-Induced Airway Hyper-Reactivity in Newborn Rats. Pediatr Res 68, 70–74 (2010). https://doi.org/10.1203/PDR.0b013e3181e0cd97
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DOI: https://doi.org/10.1203/PDR.0b013e3181e0cd97
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