Up-regulation of heme oxygenase-I in alveolar macrophages of newly diagnosed asthmatics

Respir Med. 2002 Jun;96(6):418-23. doi: 10.1053/rmed.2001.1283.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asthma / enzymology*
  • Blotting, Western
  • Cells, Cultured
  • Female
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase-1
  • Humans
  • Immunohistochemistry
  • Macrophages, Alveolar / enzymology*
  • Male
  • Membrane Proteins
  • Middle Aged
  • Sputum / chemistry
  • Up-Regulation

Substances

  • Membrane Proteins
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1