Expression of heme oxygenase isoenzymes 1 and 2 in normal and asthmatic airways - Effect of inhaled corticosteroids

Heme oxygenase (HO) is considered to be an antioxidant enzyme that cataboli zes heme to produce carbon monoxide (CO) and biliverdin. We determined the expression and distribution of HO-1 and HO-2, two isoenzymes of HO, in the airways of patients with asthma, and determined the effect of inhaled corti costeroid therapy. Immunostaining for both enzymes was widely distributed i n the airways' submucosa, particularly in airway epithelium and submucosal macrophages (CD68(+)) as determined by double immunostaining. There was no difference in intensity and extent of staining in biopsies from normal subj ects (n = 10) and subjects with asthma (n = 10). Following 1 mo of treatmen t with inhaled corticosteroids (budesonide 1,600 mug/d), there was no signi ficant change in the expression and distribution of either HO-1 or HO-2 in the airways' submucosa in eight subjects with mild asthma, despite a signif icant reduction in airway eosinophils and a reduction in bronchial responsi veness to methacholine. Levels of exhaled nitric oxide were significantly r educed, but exhaled CO levels remained unchanged by the treatment. Treatmen t with a placebo inhaler (n = 8) had no effects on these parameters. Thus, both HO-1 and HO-2 are extensively distributed equally in normal subjects a nd subjects with asthma, and are not modulated by inhaled corticosteroid th erapy in subjects with asthma. HO may be an important endogenous antioxidan t enzyme.