Transient Exposure of Pulmonary Surfactant to Hyaluronan Promotes Structural and Compositional Transformations into a Highly Active State

López-Rodríguez, Elena; Cruz, Antonio; Richter, Ralf P.; Taeusch, H. William; Pérez‐Gil, Jesús

doi:10.1074/jbc.m113.493957

Cited by 20 publications

(23 citation statements)

References 52 publications

(78 reference statements)

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“…It was therefore concluded that the reversion mechanism is somehow general for surfactants and not specific for the inhibitory agents tested. Further studies concluded that exposure to polymers above concentration thresholds at which polymer chains entangle causes substantial changes in surfactant membrane structure [ 38 ]. These changes include extensive packing, dehydration and structural depuration ending in a highly active structure able to overpass inhibition by serum or meconium.…”

Section: Discussionmentioning

confidence: 99%

Inhibition and counterinhibition of Surfacen, a clinical lung surfactant of natural origin

et al. 2018

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Inactivation of pulmonary surfactant by different components such as serum, cholesterol or meconium contributes to severe respiratory pathologies through destabilization and collapse of airspaces. Recent studies have analyzed in detail how the interfacial properties of natural surfactant purified from animal lungs are altered as a consequence of its exposure to serum proteins or meconium-mobilized cholesterol. It has been also demonstrated that pre-exposure of surfactant to polymers such as hyaluronic acid provides resistance to inactivation by multiple inhibitory agents. In the current work, we have extended these studies to the analysis of Surfacen, a clinical surfactant currently in use to rescue premature babies suffering or at risk of respiratory distress due to congenital lack of surfactant. This surfactant is also strongly inhibited by both meconium and serum when tested in the captive bubble surfactometer (CBS) under conditions mimicking respiratory dynamics. As it occurs with native surfactant, Surfacen is markedly protected from inhibition by pre-exposure to hyaluronic acid, confirming that clinical surfactants can be improved to treat pathologies associated with strongly deactivating contexts, such as those associated with lung injury and inflammation. Remarkably, we found that, under physiologically-mimicking conditions, a cholesterol-free clinical surfactant such as Surfacen is less susceptible to inhibition by cholesterol-mobilizing environments than cholesterol-containing natural surfactant, as a consequence of a markedly reduced susceptibility to incorporation of exogenous cholesterol.

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Section: Discussionmentioning

confidence: 99%

Inhibition and counterinhibition of Surfacen, a clinical lung surfactant of natural origin

et al. 2018

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“…The biological plausibility and empirical evidence of the inhibition of lung surfactant function by inhaled substances or by blood components reaching the alveolar airspaces, are high. Studies have been conducted for a number of substances including airborne nanoparticles ( Chen et al, 2017 , Yang et al, 2018 , Larsen et al, 2020 ), airborne chemicals ( Da Silva et al, 2021 ), and biological components such as albumin, cholesterol meconium, and serum ( Zuo et al, 2006 , Lopez-Rodriguez et al, 2011 , Lopez-Rodriguez et al, 2012 , Lopez-Rodriguez et al, 2013 , Zhang et al, 2012 , Autilio et al, 2021 , Gómez-Gil et al, 2009 , Lugones et al, 2018 , Gunasekara et al, 2005 ). For impregnation spray products, the inhibition of lung surfactant function has been reported across multiple methods in vitro , such as the lung surfactant bioassay ( Sørli et al, 2018 ), the capillary surfactometer ( Sørli et al, 2016 ), the pulsating bubble surfactometer ( Tashiro et al, 1998 ), and the Langmuir trough ( Duch et al, 2014 , Larsen, et al, 2014 ).…”

Section: Biological Applicability Domain Of Aop 302mentioning

confidence: 99%

An adverse outcome pathway for lung surfactant function inhibition leading to decreased lung function

Silva

Vogel

Hougaard

et al. 2021

Current Research in Toxicology

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“…However, these interactions are so far basically unexplored although a direct topographical relationship is obvious (Figure 1). One main component of the glycocalyx, hyaluronan, known to be secreted by AEII cells in vitro [27,28], has been shown to improve the biophysical (surface tension reducing) activity of surfactant in vitro and in vivo [29][30][31][32]. Thus, hyaluronan may have therapeutic potential in lung diseases where surfactant inactivation is a major pathophysiological event.…”

Section: Interactions Between Surfactant and The Glycocalyxmentioning

confidence: 99%

On Top of the Alveolar Epithelium: Surfactant and the Glycocalyx

Ochs

Hegermann

López-Rodríguez

et al. 2020

IJMS

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Gas exchange in the lung takes place via the air-blood barrier in the septal walls of alveoli. The tissue elements that oxygen molecules have to cross are the alveolar epithelium, the interstitium and the capillary endothelium. The epithelium that lines the alveolar surface is covered by a thin and continuous liquid lining layer. Pulmonary surfactant acts at this air-liquid interface. By virtue of its biophysical and immunomodulatory functions, surfactant keeps alveoli open, dry and clean. What needs to be added to this picture is the glycocalyx of the alveolar epithelium. Here, we briefly review what is known about this glycocalyx and how it can be visualized using electron microscopy. The application of colloidal thorium dioxide as a staining agent reveals differences in the staining pattern between type I and type II alveolar epithelial cells and shows close associations of the glycocalyx with intraalveolar surfactant subtypes such as tubular myelin. These morphological findings indicate that specific spatial interactions between components of the surfactant system and those of the alveolar epithelial glycocalyx exist which may contribute to the maintenance of alveolar homeostasis, in particular to alveolar micromechanics, to the functional integrity of the air-blood barrier, to the regulation of the thickness and viscosity of the alveolar lining layer, and to the defence against inhaled pathogens. Exploring the alveolar epithelial glycocalyx in conjunction with the surfactant system opens novel physiological perspectives of potential clinical relevance for future research.

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Transient Exposure of Pulmonary Surfactant to Hyaluronan Promotes Structural and Compositional Transformations into a Highly Active State

Cited by 20 publications

References 52 publications

Inhibition and counterinhibition of Surfacen, a clinical lung surfactant of natural origin

Inhibition and counterinhibition of Surfacen, a clinical lung surfactant of natural origin

An adverse outcome pathway for lung surfactant function inhibition leading to decreased lung function

On Top of the Alveolar Epithelium: Surfactant and the Glycocalyx

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