TNF-α Potentiates Oxidant and Reperfusion-Induced Endothelial Cell Injury

Gilmont, Robert R.; Dardano, Anthony N.; Engle, Jennifer; Adamson, Belinda; Welsh, Michael J.; Li, Tiedong; Remick, Daniel G.; Smith, David J.; Rees, Riley S.

doi:10.1006/jsre.1996.0101

Cited by 50 publications

(50 citation statements)

References 3 publications

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“…Similarly, other studies have clearly established a role for TNF-␣ in mediating both local and systemic inflammation after I/R injury in several vascular beds (e.g., Refs. 13,30,31). In contrast to these findings and to the lack of a role of the translocation of bacteria/bacterial products, germ-free mice presented little evidence of local or systemic injury after intestinal I/R.…”

Section: Discussionmentioning

confidence: 71%

“…Several mediators of the inflammatory process have been shown to participate in the cascade of events leading to ischemia and reperfusion (I/R) 3 injury, including CXC chemokines, platelet-activating factor and cytokines, especially TNF-␣ and IL-10 (5-12). Treatment of animals with anti-TNF-␣ Abs or experiments in TNF-␣ receptor 1-deficient animals (TNFR1 Ϫ/Ϫ ) clearly show a central role of TNF-␣ in mediating tissue injury, systemic inflammation, and lethality following intestinal reperfusion injury (6,7,13). As TNF-␣ release and action is central in the pathogenesis of the local and systemic inflammatory response that occurs after intestinal reperfusion, a greater understanding of the mediators that induce or modulate TNF-␣ production in this process is clearly of interest.…”

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confidence: 99%

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The Essential Role of the Intestinal Microbiota in Facilitating Acute Inflammatory Responses

Souza

Vieira²,

Soares³

et al. 2004

The Journal of Immunology

216

195

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The restoration of blood flow, i.e., reperfusion, is the treatment of choice to save viable tissue following acute ischemia of a vascular territory. Nevertheless, reperfusion can be accompanied by significant inflammatory events that limit the beneficial effects of blood flow restoration. To evaluate the potential role of the intestinal microbiota in facilitating the development of tissue injury and systemic inflammation, germ-free and conventional mice were compared in their ability to respond to ischemia and reperfusion injury. In conventional mice, there was marked local (intestine) and remote (lung) edema formation, neutrophil influx, hemorrhage, and production of TNF-α, KC, MIP-2, and MCP-1. Moreover, there was an increase in the concentration of serum TNF-α and 100% lethality. In germ-free mice, there was no local, remote, or systemic inflammatory response or lethality after intestinal ischemia and reperfusion and, in contrast to conventional mice, germ-free animals produced greater amounts of IL-10. Similar results were obtained after administration of LPS, i.e., little production of TNF-α or lethality and production of IL-10 after LPS in germ-free mice. Blockade of IL-10 with Abs induced marked inflammation and lethality in germ-free mice after ischemia and reperfusion or LPS administration, demonstrating that the ability of these mice to produce IL-10 was largely responsible for their “no inflammation” phenotype. This was consistent with the prevention of reperfusion-associated injury by the exogenous administration of IL-10 to conventional mice. Thus, the lack of intestinal microbiota is accompanied by a state of active IL-10-mediated inflammatory hyporesponsiveness.

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Section: Discussionmentioning

confidence: 71%

mentioning

confidence: 99%

The Essential Role of the Intestinal Microbiota in Facilitating Acute Inflammatory Responses

Souza

Vieira²,

Soares³

et al. 2004

The Journal of Immunology

216

195

View full text Add to dashboard Cite

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“…The morphological response of the endothelium to LIRI is initially apoptotic, indicated by cellular rounding and contraction, rather than necrotic (74). Other histological markers include alveolar capillary interstitial edema, hyaline membranization along alveolar ducts, and infiltration from neutrophils, macrophages, and polymorphonuclear cells.…”

Section: Morphological Changes During Lung Irmentioning

confidence: 99%

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

Hengst

Gielis

Lin

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

316

280

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Lung ischemia-reperfusion injury remains one of the major complications after cardiac bypass surgery and lung transplantation. Due to its dual blood supply system and the availability of oxygen from alveolar ventilation, the pathogenetic mechanisms of ischemia-reperfusion injury in the lungs are more complicated than in other organs, where loss of blood flow automatically leads to hypoxia. In this review, an extensive overview is given of the molecular and cellular mechanisms that are involved in the pathogenesis of lung ischemia-reperfusion injury and the possible therapeutic strategies to reduce or prevent it. In addition, the roles of neutrophils, alveolar macrophages, cytokines, and chemokines, as well as the alterations in the cell-death related pathways, are described in detail. pulmonary; lung transplantation; ventilated ischemia IN THE PAST, THE LUNG WAS thought to be relatively resistant to ischemia because of its dual circulation and the availability of oxygen from alveolar ventilation. However, the depletion of lung oxygenation by stopping the ventilation leads to the same degree of lung impairment as a decrease in mechanotransduction by loss of blood flow, as determined by increases in vascular pressure and permeability (11), indicating that any deficiency from oxygenation or mechanotransduction can have significant repercussions (149).Reperfusion of the ischemic lung is a double-edged sword. Reestablishing the perfusion of the ischemic lung is absolutely required to maintain the viability of the lung, but reperfusion itself can trigger a complex cascade of events, the so-called pulmonary ischemia-reperfusion injury (LIRI) (48), characterized by increased microvascular permeability (Pvasc), increased pulmonary vascular resistance (PVR), pulmonary edema, impaired oxygenation, and pulmonary hypertension. Ischemia of the lung, without loss of ventilation, results in a complex pathophysiological situation and, therefore, is not comparable with ischemia in other organs. During ventilated ischemia, for example, the adenosine triphosphate (ATP) levels remain normal while reactive oxygen species (ROS) are formed (70), illustrating aspects of complexity of the pathophysiology of ventilated and anoxic lung ischemia. Therefore, a distinction should be made between ventilated ischemia, meaning a loss of blood flow, and anoxia/reoxygenation, indicating the loss of oxygenation and/or perfusion. In this review, the terms anoxia/reoxygenation and ventilated ischemia will be used, if the specific model is known and/or the mechanism is suggested to be model specific. Ischemia alone will be used, if it applies for both mechanisms, if the specific model is not known, or the research involves other organs.Complete and prolonged lung anoxia for up to several hours is unavoidable during lung transplantation, with dire consequences. Reperfusion of the transplanted lung can lead to nonspecific alveolar damage, pulmonary edema, and hypoxemia within 72 h after lung transplantation. Even with the advancements in lung preservati...

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“…Several mediators and cell types of the inflammatory response are involved in the cascade of events triggered by ischemia and reperfusion (Gilmont et al, 1996;Willerson, 1997;Souza et al, 2002;Merchant et al, 2003;Sroga et al, 2003). Among the cell types participating in such tissue injury, neutrophils play a major role (Willerson, 1997).…”

mentioning

confidence: 99%

Reparixin, an Inhibitor of CXCR2 Function, Attenuates Inflammatory Responses and Promotes Recovery of Function after Traumatic Lesion to the Spinal Cord

Gorio¹,

Madaschi²,

Zadra³

et al. 2007

J Pharmacol Exp Ther

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It has been shown that the blockade of CXCR1 and CXCR2 receptors prevents ischemia/reperfusion damage in several types of vascular beds. Reparixin is a recently described inhibitor of human CXCR1/R2 and rat CXCR2 receptor activation. We applied reparixin in rats following traumatic spinal cord injury and determined therapeutic temporal and dosages windows. Treatment with reparixin significantly counteracts secondary degeneration by reducing oligodendrocyte apoptosis, migration to the injury site of neutrophils and ED-1-positive cells. The observed preservation of the white matter might also be secondary to the enhanced proliferation of NG2-positive cells. The expression of macrophage-inflammatory protein-2, tumor necrosis factor-␣, interleukin (IL)-6, and IL-1␤ was also counteracted, and the proliferation of glial fibrillary acidic protein-positive cells was markedly reduced. These effects resulted in a smaller post-traumatic cavity and in a significantly improved recovery of hind limb function. The best beneficial outcome of reparixin treatment required 7-day administration either by i.p. route (15 mg/kg) or subcutaneous infusion via osmotic pumps (10 mg/kg), reaching a steady blood level of 8 g/ml. Methylprednisolone was used as a reference drug; such treatment reduced cytokine production but failed to affect the rate of hind limb recovery.

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TNF-α Potentiates Oxidant and Reperfusion-Induced Endothelial Cell Injury

Cited by 50 publications

References 3 publications

The Essential Role of the Intestinal Microbiota in Facilitating Acute Inflammatory Responses

The Essential Role of the Intestinal Microbiota in Facilitating Acute Inflammatory Responses

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

Reparixin, an Inhibitor of CXCR2 Function, Attenuates Inflammatory Responses and Promotes Recovery of Function after Traumatic Lesion to the Spinal Cord

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