Effect of cholesterol on the physical properties of pulmonary surfactant films: Atomic force measurements study

Leonenko, Zoya; Finot, Éric; Vassiliev, V.; Amrein, Matthias

doi:10.1016/j.ultramic.2006.02.007

Cited by 29 publications

(21 citation statements)

References 47 publications

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“…The potential molecular mechanism by which increased levels of cholesterol affect the surface tension reducing ability of surfactant during compression stems mostly from reconstitution studies with high amounts of cholesterol added to exogenous surfactant preparations (8,12,13,18,19). Consistent with our results, addition of 20% cholesterol (by weight) to an exogenous surfactant preparation resulted in an inability to achieve low MST values during the compression phase of dynamic cycling.…”

Section: Discussionsupporting

confidence: 82%

“…Consistent with our results, addition of 20% cholesterol (by weight) to an exogenous surfactant preparation resulted in an inability to achieve low MST values during the compression phase of dynamic cycling. In addition, atomic force microscopy of the surface films demonstrated that high cholesterol alters the lateral organization of surfactant (18,19). Specifically, these studies, as well as other experiments with pure lipid films, demonstrated that supraphysiological levels of cholesterol increase surfactant rigidity due to the interaction of cholesterol with more fluid-like lipids (such as the unsaturated lipids of surfactant) (29,43).…”

Section: Discussionmentioning

confidence: 65%

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Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Vockeroth¹,

Gunasekara

Amrein

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical ventilation may lead to an impairment of the endogenous surfactant system, which is one of the mechanisms by which this intervention contributes to the progression of acute lung injury. The most extensively studied mechanism of surfactant dysfunction is serum protein inhibition. However, recent studies indicate that hydrophobic components of surfactant may also contribute. It was hypothesized that elevated levels of cholesterol significantly contribute to surfactant dysfunction in ventilation-induced lung injury. Sprague-Dawley rats (n = 30) were randomized to either high-tidal volume or low-tidal volume ventilation and monitored for 2 h. Subsequently, the lungs were lavaged, surfactant was isolated, and the biophysical properties of this isolated surfactant were analyzed on a captive bubble surfactometer with and without the removal of cholesterol using methyl-beta-cyclodextrin. The results showed lower oxygenation values in the high-tidal volume group during the last 30 min of ventilation compared with the low-tidal volume group. Surfactant obtained from the high-tidal volume animals had a significant impairment in function compared with material from the low-tidal volume group. Removal of cholesterol from the high-tidal volume group improved the ability of the surfactant to reduce the surface tension to low values. Subsequent reconstitution of high-cholesterol values led to an impairment in surface activity. It is concluded that increased levels of cholesterol associated with endogenous surfactant represent a major contributor to the inhibition of surfactant function in ventilation-induced lung injury.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 65%

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Vockeroth¹,

Gunasekara

Amrein

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

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“…Being a minor lipid component with limited analysis in the past, the role of cholesterol in pulmonary surfactant has attracted significant attention in recent years [40, 44,46,64,84]. Our data suggest that a cholesterol content as low as 2–3% (as in BLES) can induce significant variation in surfactant films, including formation of cholesterol-mediated phospholipid phases, variation of film fluidity and collapse mechanism.…”

Section: Discussionmentioning

confidence: 77%

“…Our data suggest that a cholesterol content as low as 2–3% (as in BLES) can induce significant variation in surfactant films, including formation of cholesterol-mediated phospholipid phases, variation of film fluidity and collapse mechanism. Although cholesterol at a supraphysiological level exhibits significant inhibition on surfactant function, cholesterol at the physiological level or lower appears not to affect the surface tension lowering ability [46, 50,64,84,85]. Therefore, cholesterol-free surfactant preparations might be more efficacious for treating certain conditions such as ARDS, in which an elevated level of cholesterol is found in the bronchoalveolar lavage fluid of these patients [86, 87].…”

Section: Discussionmentioning

confidence: 99%

Comparative study of clinical pulmonary surfactants using atomic force microscopy

Zou

Fan

Wang

et al. 2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

108

235

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Clinical pulmonary surfactant is routinely used to treat premature newborns with respiratory distress syndrome, and has shown great potential in alleviating a number of neonatal and adult respiratory diseases. Despite extensive study of chemical composition, surface activity, and clinical performance of various surfactant preparations, a direct comparison of surfactant films is still lacking. In this study, we use atomic force microscopy to characterize and compare four animal-derived clinical surfactants currently used throughout the world, i.e., Survanta, Curosurf, Infasurf and BLES. These modified-natural surfactants are further compared to dipalmitoyl phosphatidylcholine (DPPC), a synthetic model surfactant of DPPC:palmitoyl-oleoyl phosphatidylglycerol (POPG) (7:3), and endogenous bovine natural surfactant. Atomic force microscopy reveals significant differences in the lateral structure and molecular organization of these surfactant preparations. These differences are discussed in terms of DPPC and cholesterol contents. We conclude that all animal-derived clinical surfactants assume a similar structure of multilayers of fluid phospholipids closely attached to an interfacial monolayer enriched in DPPC, at physiologically relevant surface pressures. This study provides the first comprehensive survey of the lateral structure of clinical surfactants at various surface pressures. It may have clinical implications on future application and development of surfactant preparations.

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“…Stronger evidence exists for the notion that elevated cholesterol leads to surfactant dysfunction. For example, adding supraphysiological amounts of cholesterol to exogenous surfactant preparations inhibits surfactant function [35,41-43] and lateral organization [35,44,45]. …”

Section: Discussionmentioning

confidence: 99%

A ToF-SIMS study of the lateral organization of lipids and proteins in pulmonary surfactant systems

Keating

Waring

Walther

et al. 2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Pulmonary surfactant is a complex lipid–protein mixture whose main function is to reduce the surface tension at the air–liquid interface of alveoli to minimize the work of breathing. The exact mechanism by which surfactant monolayers and multilayers are formed and how they lower surface tension to very low values during lateral compression remains uncertain. We used time-of-flight secondary ion mass spectrometry to study the lateral organization of lipids and peptide in surfactant preparations ranging in complexity. We show that we can successfully determine the location of phospholipids, cholesterol and a peptide in surfactant Langmuir–Blodgett films and we can determine the effect of cholesterol and peptide addition. A thorough understanding of the lateral organization of PS interfacial films will aid in our understanding of the role of each component as well as different lipid–lipid and lipid–protein interactions. This may further our understanding of pulmonary surfactant function.

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Effect of cholesterol on the physical properties of pulmonary surfactant films: Atomic force measurements study

Cited by 29 publications

References 47 publications

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Comparative study of clinical pulmonary surfactants using atomic force microscopy

A ToF-SIMS study of the lateral organization of lipids and proteins in pulmonary surfactant systems

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