Spatial coordination of cell-adhesion molecules and redox cycling of iron in the microvascular inflammatory response to pulmonary injury.
Transmigration of phagocytic leukocytes (PLCs) from the peripheral blood into injured lung requires a conversion of the microvascular endothelial cells (ECs) to the proinflammatory phenotypes and spatiotemporal interplay of different types of cell adhesion molecules (CAMs) on PLC and endothelium. The present report is focused on involvement of iron-dependent redox signaling in spatial coordination of lung CAM due to either a pulmonary trauma or endotracheal iron administration in rats. Redox alterations, deposition of 3-nitrotyrosine, expression of VE-cadherin, ICAM-1, and the PLC integrins, and the status of thioredoxin, Ref-1, NF-kappaB and Nrf2 redox-sensitive elements in the alveolar microvasculature were assessed with EPR spectroscopy, immunobloting, and confocal microscopy. We demonstrated for the first time in vivo that the presence of catalytically active iron, deposition of myeloperoxidase, and induction of the oxidative stress in the lung-injury models were accompanied by (a) downregulation of VE-cadherin, (b) upregulation and polarization of ICAM-1 and the PLC integrins, and (c) nuclear translocation and interaction of thioredoxin, Ref-1, and NF-kappaB and complex structural changes in EC and PLC at the sites of their contacts. The studies suggested that a part of the proinflammatory action of iron in the lung resulted from its stimulation of the redox-sensitive factors.
Gorbunov
Nikolai V
NV
Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA. nikolai.gorbunov@na.amedd.army.mil
Das
Dipak K
DK
Goswami
Shyamal K
SK
Gurusamy
Narasimman
N
Atkins
James L
JL
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1; D007501:Iron; D016328:NF-kappa B; D009195:Peroxidase; D013879:Thioredoxins; D000099152:Cadherin 5; C470319:Apex1 protein, rat