HFE gene variants and iron-induced oxygen radical generation in idiopathic pulmonary fibrosis

Autor: Federica Sangiuolo, Francesca Mariani, Ermanno Puxeddu, Alessia Comandini, Giovanni Simonetti, Marco Pallante, Monica Losi, Cesare Saltini, Gabriella Pezzuto, Francesco Cavalli, Gianluigi Sergiacomi, Augusto Orlandi, Donato Di Pierro, Massimo Amicosante, A. Bisetti, Andrea Magrini, Giuliana Longo, Maurizio Zompatori, Daniela Fraboni
Přispěvatelé: Sangiuolo F, Puxeddu E, Pezzuto G, Cavalli F, Longo G, Comandini A, Di Pierro D, Pallante M, Sergiacomi G, Simonetti G, Zompatori M, Orlandi A, Magrini A, Amicosante M, Mariani F, Losi M, Fraboni D, Bisetti A, Saltini C
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Adult
Male
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Iron
Settore MED/10 - Malattie dell'Apparato Respiratorio
Cell
Hemosiderin
Bronchoalveolar Lavage
Idiopathic pulmonary fibrosis
chemistry.chemical_compound
Fibrosis
Malondialdehyde
medicine
Extracellular
Humans
Fluorometry
Hemochromatosis Protein
Alleles
Chromatography
High Pressure Liquid

Inflammation
Settore MED/04 - Patologia Generale
Lung
medicine.diagnostic_test
business.industry
Macrophages
Histocompatibility Antigens Class I
Wild type
Genetic Variation
Membrane Proteins
Middle Aged
respiratory system
medicine.disease
Molecular biology
Oxygen
medicine.anatomical_structure
Bronchoalveolar lavage
chemistry
Settore MED/03 - Genetica Medica
IDIOPATHIC PULMONARY FIBROSIS
Case-Control Studies
UIP
Female
Hemochromatosis
Reactive Oxygen Species
business
Bronchoalveolar Lavage Fluid
Popis: In idiopathic pulmonary fibrosis (IPF), lung accumulation of excessive extracellular iron and macrophage haemosiderin may suggest disordered iron homeostasis leading to recurring microscopic injury and fibrosing damage.The current study population comprised 89 consistent IPF patients and 107 controls. 54 patients and 11 controls underwent bronchoalveolar lavage (BAL). Haemosiderin was assessed by Perls' stain, BAL fluid malondialdehyde (MDA) by high-performance liquid chromatography, BAL cell iron-dependent oxygen radical generation by fluorimetry and the frequency of hereditary haemochromatosis HFE gene variants by reverse dot blot hybridisation.Macrophage haemosiderin, BAL fluid MDA and BAL cell unstimulated iron-dependent oxygen radical generation were all significantly increased above controls (pversus22.4%, OR 2.35, p=0.008) and was associated with higher iron-dependent oxygen radical generation (HFE variant 107.4±56.0, HFE wild type (wt) 59.4±36.4 and controls 16.7±11.8 fluorescence units per 105BAL cells; p=0.028 HFE variantversusHFE wt, p=0.006 HFE wtversuscontrols).The data suggest iron dysregulation associated with HFE allelic variants may play an important role in increasing susceptibility to environmental exposures, leading to recurring injury and fibrosis in IPF.
Databáze: OpenAIRE