Mast cells and reactive oxygen species in citric acid-induced airway constriction.
The noncholinergic airway constriction is mediated by tachykinins, mainly neurokinin A and substance P, and this bronchoconstriction is usually enhanced during inflammatory episodes. We demonstrated previously that reactive oxygen species play an important role in capsaicin-, hyperventilation-, and citric acid (CA) inhalation-induced noncholinergic airway constriction. For understanding cellular involvement, we further investigated the relationship between mast cells, bradykinin (BK), reactive oxygen species, and noncholinergic airway constriction. Sixty-five guinea pigs were divided into seven groups: saline control; CA; BK + CA; cromolyn sodium (CS) + CA; BK + CS + CA; compound 48/80 + CA; and compound 48/80 + BK + CA. CS was used to stabilize mast cells, whereas a secretagogue, compound 48/80, was for the depletion of mast cells. Each animal was anesthetized, cannulated, paralyzed, and ventilated artificially. In control animals, CA aerosol inhalation caused decreases in dynamic compliance and forced expiratory parameters, indicating CA-induced noncholinergic airway constriction. Either CS or compound 48/80 significantly attenuated the CA-induced airway constriction. Also, we detected a significant increase in lucigenin-initiated chemiluminescence counts of the bronchoalveolar lavage sample in the BK + CA group. Furthermore, CA exposure caused an increase in bronchoalveolar lavage substance P level. Either CS or compound 48/80 prevented the above CA-induced increases in chemiluminescence and substance P. These results suggest that mast cells play an important role in CA aerosol inhalation-induced airway constriction via perhaps releasing constricting factors.
Wu
Li-Ling
LL
Department of Physiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
Lu
Fung-Jou
FJ
Lai
Yih-Loong
YL
D000166:Acridines / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D019343:Citric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D004338:Drug Combinations; D006168:Guinea Pigs; D008163:Luminescent Measurements; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000166:Acridines; D004338:Drug Combinations; D017382:Reactive Oxygen Species; C033472:10,10'-dimethyl-9,9'-biacridinium; D019343:Citric Acid; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; D004205:Cromolyn Sodium; D001920:Bradykinin