Involvement of haemoxygenase-1 in ozone-induced airway inflammation and hyperresponsiveness

Haemoxygenase catalyses the degradation of haem to bilirubin, and the induc ible form of haemoxygenase, haemoxygenase-1, is highly induced in response to oxidative stress in vitro, The effect of haemoxygenase-1 in oxidant stre ss in vivo is not known. We determined the effect of exposure to ozone on h aemoxygenase-1 expression, and the modulation of haemoxygenase-1 expression on ozone-induced lung neutrophilia and bronchial hyperresponsiveness in ra ts. Ozone caused a significant induction of lung haemoxygenase-1. Pretreatm ent of rats with haemoglobin, a potent inducer of haemoxygenase-1, resulted in a large induction of haemoxygenase-1 expression, and inhibited ozone-in duced neutrophilia and bronchial hyperresponsiveness. Tin protoporphyrin, a competitive inhibitor of haemoxygenase, reduced the expression of haemoxyg enase-1 induced by haemoglobin. It enhanced ozone-induced neutrophilia, but not the bronchial hypenesponsiveness, and reduced the protective effect of haemoglobin. Overall, there was an association between bronchial hyperresp onsiveness and the neutrophilic response. These data indicate that haemoxyg enase-1 plays an important role in modulating the effects of an oxidant, su ch as ozone in the lungs. (C) 2000 Elsevier Science B.V. All rights reserve d.