Toxic oxidant species and their impact on the pulmonary surfactant system

Putman, E.; Golde, L.M.G. Van; Haagsman, Henk P.

doi:10.1007/pl00007561

Cited by 73 publications

(71 citation statements)

References 152 publications

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“…At present, the exact mechanisms by which surfactant alterations in I/R injury occur are not completely understood. It seems likely that toxic oxidant species like free radicals, which are known to be important mediators in I/R injury [4,33], interact with surfactant components, especially the surfactant apoproteins [34,35]. Plasma proteins entering the alveolar space during intraalveolar oedema formation are also known to inactivate endogenous [4,6] as well as exogenous surfactant [36], although the authors have recently shown that surfactant alterations also occur in lung regions free of oedema, indicating that these surfactant alterations are not merely a secondary consequence of intraalveolar oedema formation [16].…”

Section: Discussionmentioning

confidence: 99%

Preservation of intraalveolar surfactant in a rat lung ischaemia/reperfusion injury model

et al. 2000

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Ischaemia/reperfusion (I/R) injury, a major problem in clinical lung transplantation, is associated with surfactant dysfunction. The present study aimed to test the hypothesis that preservation related improvements in post-ischaemic lung function are associated with improved ultrastructural preservation of pulmonary surfactant.Rat lungs were flush perfused with modified Euro-Collins solutions (ECS), stored for 2 h at 48C, and reperfused for 40 min. Lungs were preserved with conventional (ECS 115: 115 mmol . L -1 K + ), medium-K + (ECS 40: 40 mmol . L -1 K + ), or low-K + (ECS 10: 10 mmol . L -1 K + ) ECS. Functional parameters were monitored during reperfusion (n=10 per group). After reperfusion, left lungs were prepared for electron microscopical and stereological analysis of surfactant (n=5 per group).In all three experimental groups notable I/R injury developed which was lowest in ECS 40 as indicated by significantly less intraalveolar oedema, higher perfusate oxygenation, and lower peak inspiratory pressure. This was associated with a significantly superior preservation of the ultrastructure of the surface active surfactant subtype tubular myelin in ECS 40 compared with ECS 115 and ECS 10. Stereological analysis revealed that the relative amount of tubular myelin was highest in ECS 40 (mean SEM; 6.2 0.8%) compared with ECS 115 (3.0 1.0%) and ECS 10 (2.7 1.6%).Analysis of surfactant in its natural location within the organ showed that the severity of ischaemia/reperfusion injury correlates with differences in intraalveolar surfactant composition. Improved post-ischaemic respiratory function achieved by medium-K + Euro-Collins solution is associated with superior ultrastructural preservation of tubular myelin. It is concluded that the integrity of surface active tubular myelin represents an important criterion for the assessment of lung preservation quality. Eur Respir J 2000; 15: 526±531.

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Section: Discussionmentioning

confidence: 99%

Preservation of intraalveolar surfactant in a rat lung ischaemia/reperfusion injury model

et al. 2000

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“…In ALI resulting from direct lung injury, alveolar epithelial cells are the first to be altered, while ALI resulting from indirect lung injury begins with alteration of capillary endothelial cells. Intra-alveolar oedema, together with other factors, such as reactive oxygen and nitrogen species and neutrophil elastase, leads to alterations in the pulmonary surfactant system, which, in turn, lead to the decreased compliance that can be observed in ALI patients [28][29][30][31][32][33][34]. Thus, the components of the blood-air barrier and the surfactant system are primary targets in ALI and are therefore the structures that should be addressed when assessing ALI using stereology.…”

Section: Histopathological Aspects Of Alimentioning

confidence: 99%

Stereological analysis of acute lung injury

Ochs¹

2006

Eur Respir Rev

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Acute lung injury is associated with a variety of histopathological alterations, such as oedema formation, damage to the components of the blood-air barrier and impairment of the surfactant system. Stereological methods are indispensable tools with which to properly quantitate these structural alterations at the light and electron microscopic level. The stereological parameters that are relevant for the analysis of acute lung injury are reviewed in the present article.

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“…Thus, ozone toxicity is observed mostly in the lower airways. Ozone reacts with unsaturated C=C bonds, amino acids, and other chemical structures, and ozone exposure can lead to edema, inflammation, and epithelial cell damage, contributing to lung injury and pulmonary surfactant derangement (2). The components of pulmonary surfactant (a lipoprotein complex) essential for normal lung function are likely to be vulnerable to reaction with inhaled ozone.…”

mentioning

confidence: 99%

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

Wang

Umstead

Phelps

et al. 2002

Environ Health Perspect

124

197

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Ozone exposure can cause inflammation and impaired lung function. Human surfactant protein A (SP-A) may play a role in inflammation by modulating cytokine production by macrophages. SP-A is encoded by two genes, SP-A1 and SP-A2, and several allelic variants have been characterized for each gene. These allelic variants differ among themselves in amino acids that may exhibit differential sensitivity to ozone-induced oxidation and this may produce functional differences. We studied the effects of SP-A variants before and after ozone exposure on the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. These are important proinflammatory cytokines and are expressed by the macrophage-like THP-1 cells. Eight variants were expressed in vitro, characterized by gel electrophoresis, and studied. These included six single-gene SP-A alleles and two SP-A variants derived from both genes. Variants were exposed to ozone at 1 ppm for 4 hr at 37 degrees C, and we compared their ability to stimulate cytokine (TNF-alpha and IL-8) production by THP-1 cells to air-exposed and unexposed SP-A variants. We found that a) SP-A2 variants (1A, 1A(0), 1A(1) stimulate significantly more TNF-alpha and IL-8 production than SP-A1 variants (6A, 6A(2), 6A(4); b) coexpressed SP-A variants (1A(0)/6A(2), 1A(1)/6A(4) have significantly higher activity than single gene products; c) after ozone exposure, all SP-A variants showed a decreased ability to stimulate TNF-alpha and IL-8 production, and the level of the decrease varied among SP-A variants (26-48%); and d) human SP-A from patients with alveolar proteinosis exhibited a minimal decrease (18% and 12%, respectively) in its ability to stimulate TNF-alpha and IL-8 after in vitro ozone exposure. We conclude that biochemical and functional differences exist among SP-A variants, that ozone exposure modulates the ability of SP-A variants to stimulate cytokines by THP-1 cells, and that SP-As from bronchoalveolar lavage (BAL) fluid of certain alveolar proteinosis patients may be oxidized in vivo.

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Toxic oxidant species and their impact on the pulmonary surfactant system

Cited by 73 publications

References 152 publications

Preservation of intraalveolar surfactant in a rat lung ischaemia/reperfusion injury model

Preservation of intraalveolar surfactant in a rat lung ischaemia/reperfusion injury model

Stereological analysis of acute lung injury

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

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