Up-regulation of heme oxygenase-I in alveolar macrophages of newly diagnosed asthmatics.
Exhaled carbon monoxide (CO), which has been found to be elevated in asthma, is generated primarily by heme oxygenase I (HO-I), an enzyme induced by oxidant stress and cytokines. The aim of this study was to assess the distribution and expression of HO-I 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-I by immunohistochemistry. The time response of HO-I induction was examined in cultured monocytes, which are known to maturate into monocyte-derived macrophages in culture. Lung biopsies showed prominent HO-I immunoreactivity only in alveolar macrophages. Macrophages in the induced sputum of healthy controls showed no HO-I immunoreactivity, with the exception of one case. Moderate or intense HO-I immunoreactivity could be observed in alveolar macrophages in 4/5 cases with recent asthma, and 2/7 with stable asthma, but in none ofthe patients treated with systemic corticosteroids for acute exacerbation. Experiments with cultured cells revealed that HO-I was induced by oxidants within the first 24 h, but the induction was reversed during the next 48 h. HO-I is mainly expressed in alveolar macrophages of human lung. Macrophages of induced sputum show prominent but transient HO-I immunoreactivity, in untreated asthmatics, but not in asthmatics treated with corticosteroids.
Department of Internal Medicine, University of Oulu and Oulu University Hospital, Finland.
T
T
Harju
Y
Y
Soini
R
R
Pääkkö
V L
VL
Kinnula
D000328:Adult; D000368:Aged; D001249:Asthma / Q000201:enzymology*; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D013183:Sputum / Q000737:chemistry; D015854:Up-Regulation
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1