Diapedesis of Leukocytes: Antisense Oligonucleotides for Rescue

Dragun, Duska; Haller, Hermann

doi:10.1159/000020599

Cited by 11 publications

(3 citation statements)

References 69 publications

(64 reference statements)

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“…Thus, targeting adhesion molecules may help prevent ischemic damage to the kidney. Intercellular cell adhesion molecule type A (ICAM-1) deficiency or blockage has been demonstrated to provide protection from moderate renal I/R injury (120,143). Systemic moderate hypoxia alone can induce an increase in leukocyte adhesion mediated by CD11/CD18 integrins, even in the absence of complete ischemia (133,144).…”

Section: Activation Of Inflammation and Endothelial-leukocyte Interacmentioning

confidence: 99%

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Legrand

Mik

Johannes³

et al. 2008

Mol Med

237

169

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Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways' alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.

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Section: Activation Of Inflammation and Endothelial-leukocyte Interacmentioning

confidence: 99%

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Legrand

Mik

Johannes³

et al. 2008

Mol Med

237

169

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“…[11,12] Endotheliumleukocyte interactions are mediated by an increase in adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1) and P-selectin. [13] The production of endothelin-1 (ET-1) is also increased in endothelial cells during renal I/R, a mediator that promotes further dysfunction. [14] NF-KappaB has also been shown to participate in the regulation of ET-1 pathways during renal I/R.…”

Section: Introductionmentioning

confidence: 99%

Effect of Sulfasalazine on Renal Ischemia/Reperfusion Injury in Rats

et al. 2009

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Renal ischemia/reperfusion (I/R) occurs during shock and transplant procedures, greatly affecting outcome. A definitive treatment has not been found. One of the pathophysiological bases of renal I/R injury is the activation of the transcription factor nuclear factor-kappaB (NF-KappaB). We studied the effects of sulfasalazine (SFZ), a NF-kappaB inhibitor, over renal injury in a bilateral renal I/R model in rats. Ten male Wistar rats were subjected to bilateral renal I/R for 45 min followed by 24 h of reperfusion. Half of these received 100 mg/kg SFZ orally before the induction of I/R, while the others received only saline. Five rats served as sham-operated controls. At the end of the reperfusion period, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), P-selectin, tumor necrosis factor-alpha (TNF-alpha), intracellular adhesion molecule-1 (ICAM-1), and endothelin-1 (ET-1) concentrations were determined in serum, and renal samples were taken for histological evaluation. After renal I/R, AST, LDH, BUN, TNF-alpha, ICAM-1, and ET-1 serum levels were significantly increased, and tubules were severely damaged on histological analysis, compared to sham controls. SFZ treatment reduced the AST, LDH, BUN, TNF-alpha, and ET-1 elevations, as well as the tubular damage, induced by renal I/R. Serum ICAM-1 and P-selectin were unchanged. These results show that SFZ has a protective effect over renal IR injury. The modulation of adhesion molecules probably does not play a part in these effects, but TNF-alpha and ET-1 modulation could be partly responsible for the effects we observed.

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“…The potential for intervention to prevent lymphocyte recruitment in many pathological processes is suggested by recent studies in which antisense oligonucleotides to ICAM-1 prevented ischaemic reperfusion injury and delayed graft rejection in experimental renal transplantation 12. It is possible to envisage how such approaches may be applied to treating or preventing other conditions in which adhesion molecules have a pathogenic role.…”

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confidence: 99%