Systemic blood loss affects NF-kappa B regulatory mechanisms in the lungs

Moine, Pierre; Shenkar, Robert; Kaneko, Debra; Tulzo, Yves Le; Abraham, Edward

doi:10.1152/ajplung.1997.273.1.l185

Cited by 19 publications

(15 citation statements)

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“…The ability of NAC supplementation to prevent priming in this model is similar to that previously reported for CINC expression and implies that oxidant stress generated during hemorrhage/resuscitation is a significant contributor to the induction of the primed state. Studies by other investigators suggest that xanthine oxidase produced after ischemia/reperfusion may be primarily responsible for elaboration of these oxidants (50)(51)(52). A recent report demonstrated that upregulation of inducible nitric oxide synthase during the shock phase of shock/ resuscitation may be essential to the development of lung injury, a finding consistent with a conclusion that cellular events occurring during the hypoxic phase may also contribute to the primed state (53).…”

Section: Discussionsupporting

confidence: 59%

Priming for Enhanced Alveolar Fibrin Deposition after Hemorrhagic Shock

Fan

Kapùs

et al. 2000

Am J Respir Cell Mol Biol

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Hemorrhagic shock due to major trauma predisposes to the development of acute respiratory distress syndrome. Because lung fibrin deposition is one of the hallmarks of this syndrome, we hypothesized that resuscitated shock might predispose to the development of a net procoagulant state in the lung. A rodent model of shock/resuscitation followed by low-dose intratracheal lipopolysaccharide (LPS), a clinically relevant "two-hit" model, was used to test this hypothesis. Resuscitated shock primed the lungs for an increased tissue factor and plasminogen activator (PA) inhibitor-1 gene expression in response to LPS, while the fibrinolytic PA was reduced. These alterations were recapitulated in isolated alveolar macrophages, suggesting their role in the process. LPS-induced tumor necrosis factor (TNF) was also augmented in animals after antecedent shock/resuscitation, and studies using anti-TNF antibodies revealed that TNF expression was critical to the induction of the procoagulant molecules and the reduction in PA. By contrast, TNF did not appear to play an important role in neutrophil sequestration in this model, inasmuch as anti-TNF had no effect on lung neutrophil accumulation or chemokine expression. However, treatment prevented albumin leak by preventing alveolar neutrophil activation. The inclusion of the antioxidant N-acetyl-cysteine in the resuscitation fluid resulted in prevention of both the development of the net procoagulant state and lung neutrophil sequestration, suggesting a role for upstream oxidant effects in the priming process. These studies provide a cellular and molecular basis for lung fibrin deposition after resuscitated shock and demonstrate a divergence of pathways responsible for fibrin generation and neutrophil accumulation.

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Section: Discussionsupporting

confidence: 59%

Priming for Enhanced Alveolar Fibrin Deposition after Hemorrhagic Shock

Fan

Kapùs

et al. 2000

Am J Respir Cell Mol Biol

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“…In hyperoxia, increased NF-κB activation is one of the first pulmonary responses upon exposure, and this activation occurs before the detection of any proinflammatory cytokine increases [74,[138][139][140][141]. The NF-κB-binding motif is present in the promoter regions of many genes that encode proinflammatory cytokines [81,[142][143][144].…”

Section: Transcription Factors and Proinflammatory Cytokines In Hypermentioning

confidence: 99%

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

Zaher

Miller

Morrow

et al. 2007

Free Radical Biology and Medicine

121

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Mechanical ventilation with hyperoxia is necessary to treat critically ill patients. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), which can cause acute inflammatory lung injury. One of the major effects of hyperoxia is the injury and death of pulmonary epithelium, which is accompanied by increased levels of pulmonary proinflammatory cytokines and excessive leukocyte infiltration. A thorough understanding of the signaling pathways leading to pulmonary epithelial cell injury/death may provide some insights into the pathogenesis of hyperoxia-induced acute inflammatory lung injury. This review focuses on epithelial responses to hyperoxia and some of the major factors regulating pathways to epithelial cell injury/death, and proinflammatory responses upon exposure to hyperoxia. We discuss in detail some of the most interesting players, such as, NF-κB, that can modulate both proinflammatory responses and cell injury/death of lung epithelial cells. A better appreciation for the functions of these factors will no doubt help us to delineate the pathways to hyperoxic cell death and proinflammatory responses.

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“…Circulating endotoxin has been linked to the development of ALI in critically ill patients and, in experimental settings, endotoxemia results in the development of ALI (4). Similarly, hemorrhage, as a model for trauma-induced blood loss, also produces ALI (5)(6)(7). Neutrophils are an important contributory factor in the development of ALI, since the severity of pulmonary injury is decreased when neutropenia is present (8).…”

Section: Introductionmentioning

confidence: 99%