title: Inflammatory leukocytes and iron turnover in experimental hemorrhagic lung trauma.
abstract: To monitor cascade of events following alveolar extravasation of blood due to exposure to shock wave (SW), we conducted spatiotemporal assessment of myeloperoxidase (MPO), heme oxygenase 1 (HO-1), Cu,Zn superoxide dismutase (SOD-1), transferrin (TRF), 3-nitrotyrosine (3NTyr), alveolar endothelial cadherin (VE-CDH), and the CD11b adhesion molecules on leukocytes using electron microscopy, electron paramagnetic resonance spectroscopy, immunofluorescence imaging, and immunoblotting. Accumulation of HO-1, MPO, 3NTyr, and SOD-1 in HIL at the first 12 h was associated with transmigration of inflammatory leucocytes (ILK) into hemorrhagic lesions (HLs). Biodegradation of extravasated hemoglobin (exvHb) and deposition of iron in alveoli occurred at 3-56 h post-exposure and was preceded by LKC degranulation and accumulation of MPO, HO-1, and SOD-1 in HLs. These alterations were accompanied by appearance of heme and non-heme iron complexes in HLs. A significant increase in TRF-bound [Fe(3+)] (i.e., 14.6 +/- 5.3 microM vs. 4.8 +/- 2.1 microM immediately after exposure) and non-TRF complexes of [Fe(3+)] (i.e., 4.5 +/- 1.8 microM vs. < 0.3 microM immediately after exposure) occurred at 24 h post-exposure. Transmigrations of ILK, nitroxidative stress, and iron deposition in endothelial and epithelial cells were accompanied by destruction of endothelial integrity at 3 h post-exposure, and alveolar capillary network and necrotic changes in the pulmonary epithelial cells at 24-56 h post-exposure.
authors.affiliation: Division of Military Casualty Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. nikolai.gorbounov@na.amedd.army.mil
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Gorbunov
authors.forename: Lidmila V
authors.initials: LV
authors.lastname: Asher
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Ayyagari
authors.forename: James L
authors.initials: JL
authors.lastname: Atkins
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001753:Blast Injuries / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006470:Hemorrhage / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014168:Transferrin / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051547:Heme Oxygenase-1; D006454:Hemoglobins; D007501:Iron; D009195:Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014168:Transferrin; D014443:Tyrosine; D000099152:Cadherin 5; C002744:3-nitrotyrosine; C000606292:Sod1 protein, rat