lactoferrin and Hemosiderosis

Topics: Anemia, Hypochromic; Animals; Bacteria; Blood Proteins; Bone Marrow; Diet; Female; Fungi; Hemochromatosis; Hemosiderosis; Humans; Intestinal Absorption; Intestinal Mucosa; Iron; Lactoferrin; Liver; Male; Metabolism, Inborn Errors; Mice; Rabbits; Rats; Reticulocytes; Spleen; Transferrin

Bronchopulmonary dysplasia (BPD) is characterized by simplified alveolarization and arrested vascular development of the lung with associated evidence of endothelial dysfunction, inflammation, increased oxidative damage, and iron deposition. Heme oxygenase-1 (HO-1) has been reported to be protective in the pathogenesis of diseases of inflammatory and oxidative etiology. Because HO-1 is involved in the response to oxidative stress produced by hyperoxia and is critical for cellular heme and iron homeostasis, it could play a protective role in BPD. Therefore, we investigated the effect of HO-1 in hyperoxia-induced lung injury using a neonatal transgenic mouse model with constitutive lung-specific HO-1 overexpression. Hyperoxia triggered an increase in pulmonary inflammation, arterial remodeling, and right ventricular hypertrophy that was attenuated by HO-1 overexpression. In addition, hyperoxia led to pulmonary edema, hemosiderosis, and a decrease in blood vessel number, all of which were markedly improved in HO-1 overexpressing mice. The protective vascular response may be mediated at least in part by carbon monoxide, due to its anti-inflammatory, antiproliferative, and antiapoptotic properties. HO-1 overexpression, however, did not prevent alveolar simplification nor altered the levels of ferritin and lactoferrin, proteins involved in iron binding and transport. Thus the protective mechanisms elicited by HO-1 overexpression primarily preserve vascular growth and barrier function through iron-independent, antioxidant, and anti-inflammatory pathways.

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Disease Models, Animal; Ferritins; Heme Oxygenase-1; Hemosiderosis; Humans; Infant, Newborn; Iron; Lactoferrin; Lung; Mice; Mice, Transgenic; Oxygen; Pulmonary Edema

Topics: Adult; Aged; Animals; Bile; Duodenum; Female; Hematocrit; Hemosiderosis; Humans; Immune Sera; Immunoglobulin G; Intestinal Absorption; Intestinal Secretions; Intestine, Small; Iron; Iron Radioisotopes; Lactoferrin; Lactoglobulins; Male; Middle Aged; Protein Binding; Rabbits; Transferrin