Hyperoxia amplifies TNF-alpha production in LPS-stimulated human alveolar macrophages.

O’Brien-Ladner, Amy; Nelson, M. E.; Cowley, Benjamin D.; Bailey, Kirstin; Wesselius, Lewis

doi:10.1165/ajrcmb.12.3.7873193

Cited by 38 publications

(18 citation statements)

References 25 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to our work, previous studies have described increased proinflammatory responses and particularly in LPS-induced TNF-␣ production by AM following in vitro hyperoxia (19,22,54). These results are quite different from our finding of impaired LPS-induced cytokine production.…”

Section: Discussioncontrasting

confidence: 99%

Sublethal Hyperoxia Impairs Pulmonary Innate Immunity

Baleeiro

Wilcoxen

Morris

et al. 2003

The Journal of Immunology

108

View full text Add to dashboard Cite

Supplemental oxygen is often required in the treatment of critically ill patients. The impact of hyperoxia on pulmonary host defense is not well-established. We hypothesized that hyperoxia directly impairs pulmonary host defense, beyond effects on alveolar wall barrier function. C57BL/6 mice were kept in an atmosphere of >95% O2 for 4 days followed by return to room air. This exposure does not lead to mortality in mice subsequently returned to room air. Mice kept in room air served as controls. Mice were intratracheally inoculated with Klebsiella pneumoniae and followed for survival. Alveolar macrophages (AM) were harvested by bronchoalveolar lavage after 4 days of in vivo hyperoxia for ex vivo experiments. Mortality from pneumonia increased significantly in mice exposed to hyperoxia compared with infected mice in room air. Burden of organisms in the lung and dissemination of infection were increased in the hyperoxia group whereas accumulation of inflammatory cells in the lung was impaired. Hyperoxia alone had no impact on AM numbers, viability, or ability to phagocytize latex microbeads. However, following in vivo hyperoxia, AM phagocytosis and killing of Gram-negative bacteria and production of TNF-α and IL-6 in response to LPS were significantly reduced. AM surface expression of Toll-like receptor-4 was significantly decreased following in vivo hyperoxia. Thus sublethal hyperoxia increases Gram-negative bacterial pneumonia mortality and has a significant adverse effect on AM host defense function. Impaired AM function due to high concentrations of supplemental oxygen may contribute to the high rate of ventilator-associated pneumonia seen in critically ill patients.

show abstract

Section: Discussioncontrasting

confidence: 99%

Sublethal Hyperoxia Impairs Pulmonary Innate Immunity

Baleeiro

Wilcoxen

Morris

et al. 2003

The Journal of Immunology

108

View full text Add to dashboard Cite

show abstract

“…First, few Trypan blue positive signals, an indicator for loss of membrane integrity/cell death, were detected in either RAW 264.7 cells exposed to hyperoxia or alveolar macrophages (AM) isolated from hyperoxic lungs (<5%) at a similar level as those obtained from room air controls. This finding is consistent with previous studies which indicate that exposure to hyperoxia does not decrease viability of macrophages [21,22,25,43,44]. In addition, RAW 264.7 cells, exposure to 65% O 2, could still proliferate (Fig.…”

Section: Reduced Phagocytosis Of P Aeruginosa Is Not Due To Decreasesupporting

confidence: 93%

“…6B). The blunted sensitivity to hyperoxia-induced loss of cell viability is also reflected in the proinflammatory responses [43,44]. Results in Fig.…”

Section: Reduced Phagocytosis Of P Aeruginosa Is Not Due To Decreasementioning

confidence: 88%

See 1 more Smart Citation

Antioxidants preserve macrophage phagocytosis of Pseudomonas aeruginosa during hyperoxia

Morrow

Entezari-Zaher

Romashko

et al. 2007

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Pseudomonas. aeruginosa (PA) is a leading cause of nosocomial pneumonia in patients receiving mechanical ventilation with hyperoxia. Exposure to supraphysiological concentrations of reactive oxygen species during hyperoxia may result in macrophage damage that reduces their ability to phagocytose PA. We tested this hypothesis in cultured macrophage-like RAW 264.7 cells and alveolar macrophages from mice exposed to hyperoxia. Exposure to hyperoxia induced a similarly impaired phagocytosis of both the mucoid and non-mucoid forms of PA in alveolar macrophages and RAW cells. Compromised PA phagocytosis was associated with cytoskeleton disorganization and actin oxidation in hyperoxic macrophages. To test whether moderate concentrations of O 2 limit the loss of phagocytic function induced by ≥ 95% O 2 , mice and RAW cells were exposed to 65% O 2 . Interestingly, although the resulting lung injury/cell proliferation was not significant, exposure to 65% O 2 resulted in a marked reduction in PA phagocytosis that was comparable to that of ≥95% O 2 . Treatment with antioxidants, even post hyperoxic exposure, preserved actin cytoskeleton organization and phagocytosis of PA. These data suggest that hyperoxia reduces macrophage phagocytosis through effects on actin functions which can be preserved by antioxidant treatment. In addition, administration of moderate rather than higher concentrations of O 2 does not improve macrophage phagocytosis of PA.

show abstract

“…Hyperoxia may affect a variety of host biological systems, such as antioxidant enzymes (43) and cytokine production (28), through excessive production of reactive oxygen species. Several investigators have reported that hyperoxia up-regulates TNF-␣ gene and protein expression, especially after triggering stimuli (35,36,44,45). In addition, hyperoxia has been reported to induce a marked increase in message and protein levels of Fas in lungs, although Fas-deficient mice are not resistant to hyperoxia-induced lung damage itself (29).…”

Section: Discussionmentioning

confidence: 99%

Hyperoxia Mediates Acute Lung Injury and Increased Lethality in MurineLegionellaPneumonia: The Role of Apoptosis

Tateda

Deng

Moore

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Legionella pneumophila is a major cause of life-threatening pneumonia, which is characterized by a high incidence of acute lung injury and resultant severe hypoxemia. Mechanical ventilation using high oxygen concentrations is often required in the treatment of patients with L. pneumophila pneumonia. Unfortunately, oxygen itself may propagate various forms of tissue damage, including acute lung injury. The effect of hyperoxia as a cofactor in the course of L. pneumophila pneumonia is poorly understood. In this study, we show that exposure to hyperoxic conditions during the evolution of pneumonia results in a marked increase in lethality in mice with Legionella pneumonia. The enhanced lethality was associated with an increase in lung permeability, but not changes in either lung bacterial burden or leukocyte accumulation. Interestingly, accelerated apoptosis as evidenced by assessment of histone-DNA fragments and caspase-3 activity were noted in the infected lungs of mice exposed to hyperoxia. TUNEL staining of infected lung sections demonstrated increased apoptosis in hyperoxic mice, predominantly in macrophages and alveolar epithelial cells. In vitro exposure of primary murine alveolar epithelial cells to Legionella in conjunction with hyperoxia accelerated apoptosis and loss of barrier function. Fas-deficient mice demonstrated partial resistance to the lethal effects of Legionella infection induced by hyperoxia, which was associated with attenuated apoptosis in the lung. These results demonstrate that hyperoxia serves as an important cofactor for the development of acute lung injury and lethality in L. pneumophila pneumonia. Exaggerated apoptosis, in part through Fas-mediated signaling, may accelerate hyperoxia-induced acute lung injury in Legionella pneumonia.

show abstract

Hyperoxia amplifies TNF-alpha production in LPS-stimulated human alveolar macrophages.

Cited by 38 publications

References 25 publications

Sublethal Hyperoxia Impairs Pulmonary Innate Immunity

Sublethal Hyperoxia Impairs Pulmonary Innate Immunity

Antioxidants preserve macrophage phagocytosis of Pseudomonas aeruginosa during hyperoxia

Hyperoxia Mediates Acute Lung Injury and Increased Lethality in MurineLegionellaPneumonia: The Role of Apoptosis

Contact Info

Product

Resources

About