Mast cells mediate hyperoxia-induced airway hyper-reactivity in newborn rats.
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.
Schultz
Eric D
ED
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Potts
Erin N
EN
Mason
Stanley N
SN
Foster
William M
WM
Auten
Richard L
RL
D000818:Animals; D000831:Animals, Newborn; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001549:Benzamides; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D005260:Female; D018496:Hyperoxia / Q000378:metabolism*; D000068877:Imatinib Mesylate; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D016210:Methacholine Chloride / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration
D018927:Anti-Asthmatic Agents; D001549:Benzamides; D016085:Bronchoconstrictor Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016210:Methacholine Chloride; D000068877:Imatinib Mesylate; D004205:Cromolyn Sodium
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