Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A

Visseren, Frank L.J.; Verkerk, M.S.A.; Bruggen, Tjomme van der; Marx, Joannes J.M.; Asbeck, B. S. Van; Diepersloot, R.J.A.

doi:10.1046/j.1365-2362.2002.0320s1084.x

Cited by 59 publications

(51 citation statements)

References 39 publications

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“…1 Iron in vitro has been shown to upregulate interleukin-6 production by HUVECs, 42 whereas iron chelators inhibit the tumor necrosis factor-␣-mediated upregulation of endothelial adhesion molecules. 43,44 In iron overload diseases with 100% transferrin saturation, such as hemochromatosis, a labile form of iron may exist.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Labile Iron Modulates Adhesion of Human Monocytes to Human Endothelial Cells

Kartikasari

Georgiou

Visseren

et al. 2004

ATVB

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Objective-Elevated iron stores and high plasma iron concentration have been linked to an increased risk of atherosclerosis.Iron may thereby affect the interaction of monocytes to endothelium, an initial event in the formation of atherosclerotic plaques. Methods and Results-Addition of 10 mol/L non-transferrin-bound iron to the incubation medium caused a 2-fold increase in monocyte adhesion to human umbilical vein endothelial cells (HUVECs). A concordant increase in the expression of the following adhesion molecules was observed: vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and endothelial selectin on HUVECs as well as very late antigen-4, and lymphocyte function-associated antigen-1 on monocytes. The inclusion of either deferiprone or salicylaldehyde isonicotinoylhydrazone counteracted these effects. Intracellular iron chelation by deferoxamine was completed only after 10 hours of incubation, shown by reversal of iron-quenched intracellular calcein signal, and concurrently the effects of iron were blunted. The membrane-impermeable chelator, diethylenetriamine pentaaceticacid, failed to negate iron effects, even after 48 hours of treatment. Furthermore, only membrane-permeable superoxide or hydroxyl radical scavengers were capable of preventing HUVEC activation by iron. Conclusions-Non-transferrin-bound iron increases the level of intracellular labile iron, which promotes monocyte recruitment to endothelium and may thereby contribute to the pathogenesis of atherosclerosis. Iron-induced adhesion molecule expression was observed, and this event may involve the production of oxygen radicals. Key Words: iron Ⅲ atherosclerosis Ⅲ monocytes Ⅲ endothelium Ⅲ adhesion molecules A therosclerosis has been associated with several important environmental and genetic risk factors. It is characterized by inflammatory changes leading to plaque formation and, furthermore, to plaque rupture and arterial thrombosis. Transendothelial migration of leukocytes is a fundamental inflammatory mechanism in atherogenesis. 1 This process is partly mediated by the interaction between endothelial adhesion molecules and their ligands on monocytes.Elevated concentrations of adhesion molecules have been observed in human atherosclerotic plaques, including 2 members of the immunoglobulin superfamily of adhesion receptors, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as a member of the selectin family, endothelial selectin (E-Selectin). Moreover, a significant correlation has been found between the degree of macrophage infiltration and endothelial ICAM-1, VCAM-1, and E-selectin expression in atherosclerotic lesions. 2 The infiltration of leukocytes consists of consecutive adhesion-mediated events. The first step of adhesion involves binding of selectins to carbohydrate ligands that triggers tethering of the leukocytes to the activated endothelium along the vessel wall. Arrest and firm adhesion of the leukocytes on activated endothelial cells occur depending on the activat...

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Section: Discussionmentioning

confidence: 99%

Intracellular Labile Iron Modulates Adhesion of Human Monocytes to Human Endothelial Cells

Kartikasari

Georgiou

Visseren

et al. 2004

ATVB

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“…OH· is highly reactive and damages non-specifically and irreversibly at its site of formation. The formation of OH· results in oxidation of proteins, DNA, and lipids as well as endothelial cell dysfunction and eventual cell death (Kvietys et al 1989;Beckman et al 1990;Visseren et al 2002).…”

Section: Additional Pro-oxidantsmentioning

confidence: 99%

“…Within an oxidative environment, Fe 2+ release contributes to the formation of OH· (Kvietys et al 1989;Visseren et al 2002). Intracellular Fe 2+ stores can be released by O 2 ·-and NO stimulation (Beckman et al 1990;Davidson et al 1997;Alderton et al 2001), this likely plays a role in OH· formation with increased metal ion availability during oxidative stress.…”

Section: Myeloperoxidase and Ironmentioning

confidence: 99%

Mechanisms of H2O2-induced oxidative stress in endothelial cells

Coyle

Martínez

Coleman

et al. 2006

Free Radical Biology and Medicine

131

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“…10 Use of these methods has identified several important effects of iron in endothelial activation and oxidative injury. 9,[11][12][13][14][15][16][17][18][19][20] But the in vitro approach does not define endothelial iron status in vivo, in particular what might represent a physiologically optimal range of endothelial iron concentrations. Iron status parameters such as serum ferritin are imperfect measures of total body iron stores and are likely to be even less adequate in assessing endothelial iron status.…”

Section: See Page 1577 Endothelial Iron Status In Vivomentioning

confidence: 99%

Stored Iron and Vascular Reactivity

Sullivan

2005

ATVB

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Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A

Cited by 59 publications

References 39 publications

Intracellular Labile Iron Modulates Adhesion of Human Monocytes to Human Endothelial Cells

Intracellular Labile Iron Modulates Adhesion of Human Monocytes to Human Endothelial Cells

Mechanisms of H2O2-induced oxidative stress in endothelial cells

Stored Iron and Vascular Reactivity

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