Heme Oxygenase-1 Expression in Human Lungs with Cystic Fibrosis and Cytoprotective Effects against Pseudomonas Aeruginosa In Vitro

• Published in: American journal of respiratory and critical care medicine 2004-09, Vol.170 (6), p.633-640
• Main Authors: Zhou, Hailan, Lu, Fuhua, Latham, Christopher, Zander, Dani S, Visner, Gary A
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies; Apoptosis; Apoptosis - immunology; Biological and medical sciences; Cell Line; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - enzymology; Cystic Fibrosis - immunology; Cystic Fibrosis - microbiology; Cytokines; Cytoprotection - immunology; Heme Oxygenase (Decyclizing) - biosynthesis; Heme Oxygenase (Decyclizing) - immunology; Heme Oxygenase-1; Humans; Infections; Inflammation; Intensive care medicine; Iron; Lung - enzymology; Lung - immunology; Lung diseases; Lung Diseases - immunology; Lungs; Medical sciences; Membrane Proteins; Oxidative stress; Oxidative Stress - immunology; Polymerase chain reaction; Pseudomonas aeruginosa - pathogenicity; Pseudomonas Infections - complications; Pseudomonas Infections - immunology; Smooth muscle
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200311-1607OC

Inflammation and oxidative stress play important roles in cystic fibrosis (CF) lung disease. Inflammatory/oxidant-mediated induction of heme oxygenase-1 (HO-1) is believed to be a cytoprotective response. This study examined HO-1 expression in lung samples from patients with CF using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. In addition, we evaluated myeloperoxidase staining as a marker of acute inflammation and potentially an increase in oxidant stress and Prussian blue and ferritin staining to assess iron status of the lung. Macrophage HO-1 staining was increased in diseased lungs as compared with normal control subjects and correlated with myeloperoxidase staining. Quantitative reverse transcription-polymerase chain reaction further supported an increase in HO-1 expression in CF lung disease. Although iron staining was minimal, ferritin staining was increased in diseased lungs in concert with HO-1 staining. To determine whether HO-1 induction was cytoprotective, we evaluated a CF airway epithelial cell line, IB3.1, in response to Pseudomonas aeruginosa-induced injury/apoptosis in cells overexpressing HO-1 by either transient or stable transfection of pcDNA3.1/HO-1 construct. Overexpression of HO-1 resulted in protection against P. aeruginosa-induced injury/apoptosis. This suggests that the induction of HO-1 in patients with CF is a cytoprotective event and that augmenting its expression is a potential therapy against bacterial injury.