Hyperoxia exposure impairs surfactant function and metabolism

Zenri, Hiromi; Rodriquez-Capote, Karina; McCaig, Lynda; Yao, Li–Juan; Brackenbury, Angela; Possmayer, Fred; Veldhuizen, Ruud A. W.; Lewis, Jaime D.

doi:10.1097/01.ccm.0000126264.00551.c8

Cited by 40 publications

(28 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with previous reports [22], our data showed that prolonged exposure to hyperoxia resulted in decreased compliance and increased inflammation within the lung, which was associated with increased levels of oxidative markers and an alteration in antioxidative metabolism. A unique aspect of our study was the detailed analysis of the surfactant system, specifically oxidized surfactant, at 2 different time points over the course of the injury.…”

Section: Discussionsupporting

confidence: 94%

“…We consider the increased LA PL levels to most likely reflect a protective measure involving enhanced surfactant secretion because it appears unlikely that LA to SA subtype conversion would be decreased in the presence of increased serum proteins within the airspace [29]. In fact, based on the present findings, we suspect that the increased serum protein levels present within the lungs of the 60-hour exposure group may have inhibited the function of surfactant LA, thereby providing the major contribution to the decreased lung compliance observed in these animals [22]. Similar observatrions were made by Dombrowski and colleagues [25].…”

Section: Discussionmentioning

confidence: 68%

“…Previous in vivo studies utilizing animal models that primarily involve oxidative damage to the lung have usually evaluated a very severe stage of injury with marked changes in lung dysfunction [22,25]. In addition, most studies have not measured levels of antioxidants in the various lung compartments at the same time as oxidative markers.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The Effects of Hyperoxia Exposure on Lung Function and Pulmonary Surfactant in a Rat Model of Acute Lung Injury

Pace

Yao

Wilson

et al. 2009

Experimental Lung Research

Self Cite

View full text Add to dashboard Cite

2 The objective of this study was to determine if prolonged hyperoxia exposure would deplete antioxidants, resulting in excessive oxidative stress that would lead to oxidation of pulmonary surfactant and contribute to lung dysfunction. Rats were exposed to either hyperoxic (>95% O 2 ) or normoxic (21% O 2 ) oxygen concentrations for 48 or 60 hours. Pulmonary compliance, inflammatory cells, and total protein levels were measured as indicators of lung injury. Bronchoalveolar lavage (BAL) samples were analyzed for surfactant composition, antioxidant content, and markers of oxidative stress. Antioxidants were also measured in lung tissue and plasma samples. Hyperoxia exposure for 60 hours resulted in increased protein and inflammatory cells in BAL, and lower pulmonary compliance, compared to all other groups. Total surfactant and surfactant large aggregates were increased following 48 hours of hyperoxia exposure, with a further increase following 60 hours. Animals exposed to 60 hours of hyperoxia also demonstrated lower ascorbate levels in lung tissue, increased lipid peroxides in BAL, and increased oxidation of phosphatidylglycerol

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

The Effects of Hyperoxia Exposure on Lung Function and Pulmonary Surfactant in a Rat Model of Acute Lung Injury

Pace

Yao

Wilson

et al. 2009

Experimental Lung Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ample literature is available that indicates breathing 100% oxygen may impair pulmonary gas exchange due to inhibition of hypoxic pulmonary vasoconstriction (38) and resorption atelectasis (38,39) in lung regions with low ventilation/perfusion ratios (40). Moreover, hyperoxic ventilation combined with high tidal volumes caused lung injury (41), similar to the damage induced by prolonged hyperoxia (Ͼ48 hrs) (42). This striking discrepancy may be due to our ventilator protocol, that is, application of PEEP levels of 12 production (open whiskers) and direct, aerobic glucose oxidation (hatched whiskers) in the control (white symbols, n ϭ 10) and hyperoxic (gray symbols, n ϭ 10) animals.…”

Section: Discussionmentioning

confidence: 84%

Effects of ventilation with 100% oxygen during early hyperdynamic porcine fecal peritonitis*

Barth

Bassi

Maybauer

et al. 2008

Critical Care Medicine

View full text Add to dashboard Cite

show abstract

“…Unlike SP-D ϩ/ϩ animals, SP-D Ϫ/Ϫ mice were able to maintain higher BAL phospholipid levels, phospholipidassociated SP-B, and surfactant function early in hyperoxic exposure. Several previous studies have shown that exposure of rodents to either prolonged periods of hyperoxia or to oxidizing agents such as paraquat to induce a relatively severe oxidative insult resulted in significant lung dysfunction that was associated with oxidative changes in endogenous surfactant (29,37,50,68) and depletion of surfactant phospholipid and surfactant proteins (35). Instillation of exogenous surfactant has been shown to attenuate the degree of alveolar injury caused by hyperoxia resulting in improved survival (51).…”

Section: Ablation Of the Sp-d Gene Results In Progressive Alveolar Prmentioning

confidence: 99%

SP-D-deficient mice are resistant to hyperoxia

Jain¹,

Atochina‐Vasserman²,

Kadire³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

surfactant protein D; inflammation; alveolar macrophages; collectin AS A BYPRODUCT OF THE USE of high oxygen (O 2 ) concentrations often required in management of patients with respiratory failure, reactive oxygen species produced during hyperoxic exposure can adversely affect the lung. It has been proposed that the balance between oxygen radical production and antioxidant capacities can modulate oxygen-mediated injury. The lung responds to hyperoxia by enhancing the expression of cytoprotective proteins including antioxidants (65), DNA repair enzymes (55), and regulators of cell survival. In addition, elevated expression of certain surfactant components occurs in lungs of adult (54) and neonatal rats (64) during adaptation to both sublethal (85%) and lethal (95%) oxygen (1).Surfactant protein D (SP-D), an airway epithelial secretory product, belongs to the superfamily of mammalian C-type (Ca 2ϩ -binding) lectins (collectins), which also includes SP-A and serum mannose-binding lectin. Like all collectins, monomeric SP-D is distinguished by the presence of an NH 2 -terminal cysteine-rich domain, a collagen domain, a coiled-coil neck domain, and a lectin domain with calcium-dependent regulatory elements. SP-D monomers associate through their collagenous domains to form a basic functional trimer, which then associates into higher order multimers. This oligomeric assembly provides high avidity, affinity, and specificity to SP-D ligand recognition. In the lung, SP-D ligands include allergens, particles, bacterial cell wall components, and viral envelope proteins (26). SP-D is also known to be chemotactic for neutrophils and mononuclear phagocytes (25) and to modulate alveolar type II (61) and macrophage function in vitro (39).SP-D is produced primarily by alveolar type II cells and nonciliated bronchiolar cells in the lung (24) and is constitutively secreted into the alveoli where it influences surfactant homeostasis (40), effector cell functions, and host defense. It is upregulated in a variety of inflammatory and infectious conditions including Pneumocystis pneumonia (5), asthma (2), and bleomycin injury (17). Mice or rats exposed to hyperoxic challenge also have increases in SP-D (13), suggesting that it may have a role in protection from this insult.Targeted disruption of the SP-D gene in vivo in two genetically different backgrounds has been shown to result in mice with increased alveolar and cellular pools of surfactant phospholipid, accelerated development of age-related emphysema, and large, foamy macrophages (14,40). These SP-D null mice (SP-D Ϫ/Ϫ ) also exhibit an increase in the baseline level of inflammation in the lung, increases in metalloproteinase activity, and biochemical evidence of enhanced oxidative-nitrative stress (4, 63). In addition, SP-D deficiency also confers susceptibility to specific bacterial (45) and viral infections (46).We have previously reported modulation of bleomycininduced lung injury by SP-D. In SP-D Ϫ/Ϫ mice, we showed increased susceptibility to bleomycin and evidence of oxida...

show abstract

Hyperoxia exposure impairs surfactant function and metabolism

Abstract: Oxidative stress on the endogenous surfactant system may represent an important mechanism contributing to the surfactant dysfunction and abnormal surfactant metabolism associated with hyperoxia-induced lung injury.

Cited by 40 publications

References 36 publications

The Effects of Hyperoxia Exposure on Lung Function and Pulmonary Surfactant in a Rat Model of Acute Lung Injury

The Effects of Hyperoxia Exposure on Lung Function and Pulmonary Surfactant in a Rat Model of Acute Lung Injury

Effects of ventilation with 100% oxygen during early hyperdynamic porcine fecal peritonitis*

SP-D-deficient mice are resistant to hyperoxia

Contact Info

Product

Resources

About