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Eur Respir J 2004; 23:652-653
Copyright ©ERS Journals Ltd 2004

Haem oxygenase-1 expression is diminished in alveolar macrophages of patients with COPD

D-J. Slebos1, H.A.M. Kerstjens1, S.R. Rutgers1, H.F. Kauffman2, A.M.K. Choi3 and D.S. Postma1

1 Depts of Pulmonary diseases, and 2 Allergology, University Hospital Groningen, the Netherlands, and 3 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA

CORRESPONDENCE:

To the Editor:

We read with great interest the paper by Maestrelli et al. 1 recently published in the European Respiratory Journal (ERJ). They showed a lower expression of haem oxygenase-1 (HO-1) in alveolar macrophages in lung tissue samples of patients with chronic obstructive pulmonary disease (COPD) than of controls. Unfortunately, the authors included a mixed group of smokers and nonsmokers. This makes their results more difficult to interpret since cigarette smoke is known to influence HO-1 expression as shown in an earlier paper by the same authors 2. Furthermore, the lung tissue samples in their COPD patient group were mainly derived by lung volume resection surgery and in the control group from resection because of lung cancer 1. We have recently analysed bronchoalveolar lavage (BAL) fluid of exsmokers with COPD and compared these to healthy exsmokers thereby ruling out the effects of current smoking history.

Thirteen patients with COPD, according to American Thoracic Society (ATS) criteria, were included with a mean age of 64 yrs, forced expiratory volume in one second (FEV1) 59% predicted, reversibility 6.0% of pred FEV1, and 26 pack-yrs of smoking. Eleven age matched control subjects were recruited, with a mean age of 58 yrs, FEV1 103% pred, reversibility 3.4% of pred FEV1, and 25 pack-yrs 3. All subjects had no history of asthma or atopy and had a negative skin test for 18 common aeroallergens. Treatment with inhaled corticosteroids was discontinued at least 1 month prior to the study and no treatment with oral corticosteroids and antibiotics was allowed in the same period. The airways were lavaged, using the first 50 mL for bronchial wash and the subsequent 150 mL for bronchoalveolar lavage as described previously 3. The lavage alveolar macrophage count was comparable in both groups. Immunostaining of cytospins was performed with a monoclonal antibody against HO-1 (Beckton Dickinson, Franklin Lakes, NJ, USA). Total HO-1 expression on macrophages was scored semi-quantitatively in a blinded panel by two independent observers; scores ranged from 0 (negative), 1, 2, to 3 (maximal) according to increasing intensity. Four hundred alveolar macrophages were counted on two slides and the HO-1 scores were added up. The overall HO-1 expression of BAL alveolar macrophages was significantly lower in the exsmoking COPD patients when compared to the healthy exsmoking controls (fig. 1Go).



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  		Fig. 1.— Total haem oxygenase-1 (HO-1) expression. Semi-quantitative total score of HO-1 expression on alveolar macrophages in bronchoalveolar lavage fluid for exsmoking chronic obstructive pulmonary disease patients ({circ}) and age-matched healthy exsmoking controls ({square}). The horizontal line represents the median. #: p=0.018.

 
The lower expression of haem oxygenase-1 in lavage macrophages observed in our patients with moderate-to-severe chronic obstructive pulmonary disease (Global initiative for Chronic Obstructive Lung Disease stage 2–3, 4) corroborates the findings of Maestrelli et al. 1 on surgical specimens. It extends their findings in that this decreased expression is also present in patients and controls without current smoking, i.e. smoking does not directly influence the haem oxygenase-1 expression. Haem oxygenase-1 has very potent anti-oxidative and anti-inflammatory capacities, for instance protection against allograft rejection and hyperbaric oxygen injury in animal models 5. The results of Maestrelli et al. 1 and our own results are compatible with the hypothesis that haem oxygenase-1 is insufficiently upregulated in chronic obstructive pulmonary disease. This might be due to genetic polymorphisms: Yamada et al. 6 for instance have shown a larger number of (GT)n repeats in the haem oxygenase-1 gene promoter to decrease inducibility of haem oxygenase-1 by reactive oxygen species. We believe that further research to elucidate the exact role of haem oxygenase-1, its genetic variability and its downstream products in chronic obstructive pulmonary disease is warranted.

References

  1. Maestrelli P, Paska C, Saetta M, et al. Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients. Eur Respir J 2003;21:971–976.[Abstract/Free Full Text]
  2. Maestrelli P, El Messlemani AH, De Fina O, et al. Increased Expression of Heme Oxygenase (HO)-1 in Alveolar Spaces and HO-2 in Alveolar Walls of Smokers. Am J Respir Crit Care Med 2001;164:1508–1513.[Abstract/Free Full Text]
  3. Rutgers SR, Timens W, Kaufmann HF, van der Mark TW, Koeter GH, Postma DS. Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD. Eur Respir J 2000;15:109–115.[Abstract]
  4. Fabbri LM, Hurd SS, GOLD Scientific Committee. Global Strategy for the Diagnosis, Management and Prevention of COPD: 2003 update. Eur Respir J 2003;22:1–2.[Free Full Text]
  5. Slebos DJ, Ryter SW, Choi AM. Heme oxygenase-1 and carbon monoxide in pulmonary medicine. Respir Res 2003;4:7.[CrossRef][Medline] [Order article via Infotrieve]
  6. Yamada N, Yamaya M, Okinaga S, et al. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet 2000;66:187–195.[CrossRef][ISI][Medline] [Order article via Infotrieve]



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