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Editorial Focus

Heme oxygenase attenuates allergen-induced airway inflammation and hyperreactivity in guinea pigs

¹Institut National de la Santé et de la Recherche Médicale U408 and ⁴Service d'Anatomie Patholologique, Hopital Bichat Institut Fédératif de Recherches 02, Faculté Xavier Bichat, 75018 Paris; ³Service de Biochimie, Hopital Kremlin-Bicêtre, Université Paris Sud, 94270 Le Kremlin Bicêtre, France; and ²Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, SW72AZ London, United Kingdom

Submitted 18 July 2003 ; accepted in final form 1 March 2004

Heme oxygenase (HO), the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases. HO is induced in airways during asthma; however, its functional role is unclear. Therefore, we evaluated the role of HO on airway inflammation [evaluated by bronchoalveolar lavage (BAL) cellularity and BAL levels of eotaxin, PGE₂, and proteins], mucus secretion (evaluated by analysis of MUC5AC gene expression and periodic acid-Schiff staining), oxidative stress (evaluated by quantification of 4-hydroxynonenal adducts and carbonylated protein levels in lung homogenates), and airway responsiveness to histamine in ovalbumin (OVA)-sensitized and multiple aerosol OVA or saline-challenged guinea pigs (6 challenges, once daily, OVA group and control group, respectively). Airway inflammation, mucus secretion, oxidative stress, and responsiveness were significantly increased in the OVA group compared with the control group. HO upregulation by repeated administrations of hemin (50 mg/kg ip) significantly decreased airway responsiveness in control animals and airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These effects were reversed by the concomitant administration of the HO inhibitor tin protoporphyrin-IX (50 µmol/kg ip). Repeated administrations of tin protoporphyrin-IX alone significantly increased airway responsiveness in control animals but did not modify airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These results suggest that upregulation of the HO pathway has a significant protective effect against airway inflammation, mucus hypersecretion, oxidative stress, and hyperresponsiveness in a model of allergic asthma in guinea pigs.

allergy; free radicals; carbon monoxide; bilirubin

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