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- Title
IRON-DEPENDENT REDOX SIGNALING AND INCREASE IN LEUKOCYTE-ENDOTELIAL INTERACTION IN A MODEL OF MICROVASCULAR INFLAMMATION IN LUNG.
- Authors
Gorbunov, Nikolai Viktor; Das, Dipak K.; Gurusamy, Narasimman; Atkins, James L.
- Abstract
Extensive oxidative stress (OS) to lung is associated with increase in microvascular permeability (MP) and inflammation culminating in acute respiratory distress syndrome. We used endotracheal administration of iron complexes with nitrilotriacetate (NTAFe) to clarify the role of OS and redox signaling (RS) in the phagocytic leukocyte (PL) sequestration and diapedesis. Induction of OS, RS, pro-inflammatory alterations in endothelium (ED), and microvascular transmigration of PL were assessed with EPR techniques, immunoblotting, histological and immunofluorescence (IF) confocal imaging. OS induced by NTAFe increased PL sequstration and MP for blood cells within 3 h post-treatment. These effects were accompanied by (i) nuclear translocation of TRX, Ref1, and Nrf2 in the alveolar cells, (ii) down-regulation of VE-cadherin, and up-regulation ICAM1 and CD18 adhesion molecules on ED cells and PL. Expression of CD18 and lysosomal LAMP1 was highest at leading edges of PL and co-localized with expression of both ICAM1 and PECAM1 on ED. Effects of NTAFe were inhibited by N,N′-bis (2-hydroxybenzyl) ethylenediamine-N,N′-diacetic acid (HBED), a polyphenolic iron chelator. We conclude that RS mediate down-regulation of barrier function and up-regulation of inflammation in microvasculature produced by OS.
- Subjects
OXIDATION-reduction reaction; LEUCOCYTES; ENDOTHELIUM; OXIDATIVE stress; INFLAMMATION; BLOOD cells
- Publication
FASEB Journal, 2007, Vol 21, Issue 5, pA128
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.5.a128-a