Involvement of haemoxygenase-1 in ozone-induced airway inflammation and hyperresponsiveness.
Haemoxygenase catalyses the degradation of haem to bilirubin, and the inducible form of haemoxygenase, haemoxygenase-1, is highly induced in response to oxidative stress in vitro. The effect of haemoxygenase-1 in oxidant stress in vivo is not known. We determined the effect of exposure to ozone on haemoxygenase-1 expression, and the modulation of haemoxygenase-1 expression on ozone-induced lung neutrophilia and bronchial hyperresponsiveness in rats. Ozone caused a significant induction of lung haemoxygenase-1. Pretreatment of rats with haemoglobin, a potent inducer of haemoxygenase-1, resulted in a large induction of haemoxygenase-1 expression, and inhibited ozone-induced neutrophilia and bronchial hyperresponsiveness. Tin protoporphyrin, a competitive inhibitor of haemoxygenase, reduced the expression of haemoxygenase-1 induced by haemoglobin. It enhanced ozone-induced neutrophilia, but not the bronchial hyperresponsiveness, and reduced the protective effect of haemoglobin. Overall, there was an association between bronchial hyperresponsiveness and the neutrophilic response. These data indicate that haemoxygenase-1 plays an important role in modulating the effects of an oxidant, such as ozone in the lungs.
Hisada
T
T
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, SW3 6LY, London, UK.
Salmon
M
M
Nasuhara
Y
Y
Chung
K F
KF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000201:enzymology*; D001991:Bronchitis / Q000139:chemically induced / Q000201:enzymology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006454:Hemoglobins / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology; D010126:Ozone / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D013047:Specific Pathogen-Free Organisms
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D010126:Ozone; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D000109:Acetylcholine