Abstract
Exhaled carbon monoxide (CO), which has been found to be elevated in asthma, is generated primarily by heme oxygenase 1 (HO-1), an enzyme induced by oxidant stress and cytokines. The aim of this study was to assess the distribution and expression of HO-1 in various human lung cells in acute and stable asthma.Normal lung tissue biopsies (from 6 non-smoking subjects operated on for a lung tumour) and macrophages from induced sputum (from 5 healthy controls, 5 untreated asthmatics, 7 stable treated asthmatics and 5 asthmatics recovering from exacerbation and being on systemic steroids) were investigated for HO-1 by immunohistochemistry. The time response of HO-1 induction was examined in cultured monocytes, which are known to maturate into monocyte-derived macrophages in culture. Lung biopsies showed prominent HO-1 immunoreactivity only in alveolar macrophages. Macrophages in the induced sputum of healthy controls showed no HO-1 immunoreactivity, with the exception of one case. Moderate or intense HO-1 immunoreactivity could be observed in alveolar macrophages in 4/5 cases with recent asthma, and 2/7 with stable asthma, but in none of the patients treated with systemic corticosteroids for acute exacerbation. Experiments with cultured cells revealed that HO-1 was induced by oxidants within the first 24 h, but the induction was reversed during the next 48 h. HO-1 is mainly expressed in alveolar macrophages of human lung. Macrophages of induced sputum show prominent but transient HO-1 immunoreactivity, in untreated asthmatics, but not in asthmatics treated with corticosteroids.
Published Version
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