Intestinal reperfusion up-regulates inducible nitric oxide synthase activity within the lung

Turnage, Richard H.; Kadesky, Kevin M.; Bartula, L.; Myers, Stuart I.

doi:10.1016/s0039-6060(05)80336-8

Cited by 52 publications

(34 citation statements)

References 18 publications

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“…Constitutive NOS is protective in IRI, whereas inducible NOS is responsible for lung dysfunction [34]. Turnage et al [37,38] demonstrated the deleterious role of inducible NOS in the lung after intestinal IRI. Matsuyama et al [39] and Kosaka et al [40] reported that COX-2 and iNOS are up-regulated and have deleterious effects on renal IRI, which is in agreement with the present results.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Lung Allergic Response by Renal Ischemia and Reperfusion Injury

Campanholle

Silva

Martins

et al. 2012

Cell Physiol Biochem

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The Th1/Th2 balance represents an important factor in the pathogenesis of renal ischemia-reperfusion injury (IRI). In addition, IRI causes a systemic inflammation that can affect other tissues, such as the lungs. To investigate the ability of renal IRI to modulate pulmonary function in a specific model of allergic inflammation, C57Bl/6 mice were immunized with ovalbumin/albumen on days 0 and 7 and challenged with an ovalbumin (OA) aerosol on days 14 and 21. After 24 h of the second antigen challenge, the animals were subjected to 45 minutes of ischemia. After 24 h of reperfusion, the bronchoalveolar lavage (BAL) fluid, blood and lung tissue were collected for analysis. Serum creatinine levels increased in both allergic and non-immunized animals subjected to IRI. However, BAL analysis showed a reduction in the total cells (46%) and neutrophils (58%) compared with control allergic animals not submitted to IRI. In addition, OA challenge induced the phosphorylation of ERK and Akt and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung homogenates. After renal IRI, the phosphorylation of ERK and expression of COX-2 and iNOS were markedly reduced; however, there was no difference in the phosphorylation of Akt between sham and ischemic OA-challenged animals. Mucus production was also reduced in allergic mice after renal IRI. IL-4, IL-5 and IL-13 were markedly down-regulated in immunized/challenged mice subjected to IRI. These results suggest that renal IRI can modulate lung allergic inflammation, probably by altering the Th1/Th2 balance and, at least in part, by changing cellular signal transduction factors.

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Section: Discussionmentioning

confidence: 99%

Modulation of Lung Allergic Response by Renal Ischemia and Reperfusion Injury

Campanholle

Silva

Martins

et al. 2012

Cell Physiol Biochem

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“…A third Ca 2ϩ -independent isoform (inducible NOS (iNOS)) is induced by inflammatory cytokines and LPS in many cell types, but mostly in monocytes/macrophages. This isoform generates high amounts of NO, which are associated with macrophage cytotoxic effects, as an essential part of normal immune mechanisms of host defense against intracellular pathogens (19,20), and in contrast, with modulatory effects on inflammatory responses (21,22).…”

mentioning

confidence: 99%

“…Production of excessive NO by macrophage iNOS has been implicated in the pathophysiology of I/R due to its role in augmenting tissue damage and cell death (14,19,20). However, the isolated effects of H/R on the expression and activity of iNOS have been scarcely studied.…”

mentioning

confidence: 99%

Hypoxia Inactivates Inducible Nitric Oxide Synthase in Mouse Macrophages by Disrupting Its Interaction with α-Actinin 4

Daniliuc

Bitterman

Rahat³

et al. 2003

The Journal of Immunology

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Nitric oxide, produced in macrophages by the high output isoform inducible NO synthase (iNOS), is associated with cytotoxic effects and modulation of Th1 inflammatory/immune responses. Ischemia and reperfusion lead to generation of high NO levels that contribute to irreversible tissue damage. Ischemia and reperfusion, as well as their in vitro simulation by hypoxia and reoxygenation, induce the expression of iNOS in macrophages. However, the molecular regulation of iNOS expression and activity in hypoxia and reoxygenation has hardly been studied. We show in this study that IFN-γ induced iNOS protein expression (by 50-fold from control, p < 0.01) and nitrite accumulation (71.6 ± 14 μM, p < 0.01 relative to control), and that hypoxia inhibited NO production (7.6 ± 1.7 μM, p < 0.01) without altering iNOS protein expression. Only prolonged reoxygenation restored NO production, thus ruling out the possibility that lack of oxygen, as a substrate, was the cause of hypoxia-induced iNOS inactivation. Hypoxia did not change the ratio between iNOS monomers and dimers, which are essential for iNOS activity, but the dimers were unable to produce NO, despite the exogenous addition of all cofactors and oxygen. Using immunoprecipitation, mass spectroscopy, and confocal microscopy, we demonstrated in normoxia, but not in hypoxia, an interaction between iNOS and α-actinin 4, an adapter protein that anchors enzymes to the actin cytoskeleton. Furthermore, hypoxia caused displacement of iNOS from the submembranal zones. We suggest that the intracellular localization and interactions of iNOS with the cytoskeleton are crucial for its activity, and that hypoxia inactivates iNOS by disrupting these interactions.

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“…For example, visceral ischemia reperfusion injury has classically been studied as an extrapulmonary cause of ALI (16,32). Because the incidence of acute kidney injury (AKI) has been reported to be 5-7% in hospitalized patients (15,30), and because the mortality rate of ALI increases from 40 -80% when it is associated with AKI (22), there is a strong interest in exploring the relationship between AKI and lung function.…”

mentioning

confidence: 99%

Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model

Dodd‐o¹,

Hristopoulos²,

Scharfstein³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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We hypothesized that the influence of acute kidney injury (AKI) on the sensitivity of the lung to an injurious process varies with the severity of the injurious process. Thus, we thought that AKI would exacerbate lung injury from low degrees of lung trauma but attenuate lung injury from higher degrees of lung trauma. C57BL/6 mice underwent AKI (30-min kidney ischemia) or sham surgery, followed at 24 h by 4 h of spontaneous breathing (SB), mechanical ventilation with low tidal volume (7 ml/kg, LTV), or mechanical ventilation with high tidal volume (30 ml/kg, HTV). Compared with LTV, median bronchoalveolar lavage (BAL) protein leak was significantly lower with SB and greater with HTV in both sham and AKI mice. Compared with LTV, median Evans blue dye-labeled albumin extravasation in lungs (L-EBD) was also significantly lower with SB and greater with HTV. L-EBD showed a significant interaction between ventilatory mode and kidney health, such that AKI attenuated the L-EBD rise seen in HTV vs. LTV sham mice. An interaction between ventilatory mode and kidney health could also be seen in BAL neutrophil number (PMN). Thus, AKI attenuated the BAL PMN rise seen in HTV vs. LTV sham mice. These data support the presence of a complex interaction between mechanical ventilation and AKI in which the sensitivity of the lung to trauma varies with the magnitude of the trauma and may involve a modification of pulmonary neutrophil activity by AKI.

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Intestinal reperfusion up-regulates inducible nitric oxide synthase activity within the lung

Cited by 52 publications

References 18 publications

Modulation of Lung Allergic Response by Renal Ischemia and Reperfusion Injury

Modulation of Lung Allergic Response by Renal Ischemia and Reperfusion Injury

Hypoxia Inactivates Inducible Nitric Oxide Synthase in Mouse Macrophages by Disrupting Its Interaction with α-Actinin 4

Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model

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