A Concentration-Dependent Mechanism by which Serum Albumin Inactivates Replacement Lung Surfactants

Warriner, Heidi E.; Ding, Junqi; Waring, Alan J.; Zasadzinski, Joseph A.

doi:10.1016/s0006-3495(02)75445-3

Cited by 80 publications

(176 citation statements)

References 34 publications

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“…This surface tension is only slightly lower than the equilibrium value of albumin alone, i.e. 54 Ϯ 1 mJ/m 2 , measured in this study and reported elsewhere (2,26). The surface tension decrease due to the addition of chitosan may indeed indicate some nonspecific electrostatic and/or hydrophilic binding between chitosan and albumin.…”

Section: Discussioncontrasting

confidence: 49%

“…A surface tension plateau at 54 Ϯ 1 mJ/m 2 is reached soon after the onset of adsorption. This plateau corresponds to the equilibrium surface tension of albumin (2,26) and indicates rapid monopolization of the air-water interface by albumin due to a competitive adsorption mechanism (2,26 -28). After approximately 300 s, the surface tension starts to slowly decrease again and eventually reaches the equilibrium value of a predominantly phospholipid film after approximately 1800 s. This second surface tension decrease from the equilibrium value of albumin to that of phospholipids indicates the replacement of albumin at the air-water interface by the lung surfactant.…”

Section: Adsorptionmentioning

confidence: 99%

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Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

et al. 2006

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ABSTRACT:Chitosan is a natural, cationic polysaccharide derived from fully or partially deacetylated chitin. Chitosan is capable of inducing large phospholipid aggregates, closely resembling the function of nonionic polymers tested previously as additives to therapeutic lung surfactants. The effects of chitosan on improving the surface activity of a dilute lung surfactant preparation, bovine lipid extract surfactant (BLES), and on resisting albumin-induced inactivation were studied using a constrained sessile drop (CSD) method. Also studied in parallel were the effects of polyethylene glycol (PEG, 10 kD) and hyaluronan (HA, 1240 kD). Both adsorption and dynamic cycling studies showed that chitosan is able to significantly enhance the surface activity of 0.5 mg/mL BLES and to resist albumin-induced inactivation at an extremely low concentration of 0.05 mg/mL, 1000 times smaller than the usual concentration of PEG and 20 times smaller than HA. Optical microscopy found that chitosan induced large surfactant aggregates even in the presence of albumin. Cytotoxicity tests confirmed that chitosan has no deleterious effect on the viability of lung epithelial cells. The experimental results suggest that chitosan may be a more effective polymeric additive to lung surfactant than the other polymers tested so far. (1) suggested the use of low-cost, water-soluble nonionic polymers, such as dextran, PEG, and polyvinylpyrrolidone (PVP), as additives to therapeutic lung surfactants. Both in vitro (1-6) and in vivo (7-9) trials have shown that these nonionic polymers can significantly improve the surface activity of different therapeutic lung surfactants and effectively reverse inactivation due to a variety of inhibitory substances.More recently, Lu et al. (10,11) reported the use of an anionic polymer, HA, as a surfactant additive. Both in vitro (10) and in vivo (11) tests showed that the addition of HA at different molecular weights to various therapeutic lung surfactants can effectively reverse serum-and meconium-induced inactivation. These studies, therefore, tentatively proved the feasibility of using an ionic polymer as a lung surfactant additive. Following these studies, we investigate here the use of a cationic polymer, chitosan, as a potential lung surfactant additive.Chitosan is a natural polysaccharide composed of linear ␤-(1¡4)-linked 2-amino-2-deoxy-␤-D-glucan combined with glycosidic linkages (12). It is derived from fully or partially deacetylated chitin, which is extracted from crustacean shells. Chitosan is also a polyelectrolyte with a positively charged backbone and is readily soluble in slightly acidic conditions (12). Chitosan was proven to be biodegradable, biocompatible, bioadhesive, and nontoxic in a range of toxicity tests (13). Because of these desirable properties, it has been extensively used in a variety of food, cosmetic, and pharmaceutical fields. Specifically, chitosan has been extensively used in drug delivery (13), including pulmonary drug delivery (12).Chan and co-workers (14 -17) have recently...

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Section: Discussioncontrasting

confidence: 49%

Section: Adsorptionmentioning

confidence: 99%

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

et al. 2006

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“…Deactivation of surfactant by serum components and by inflammatory mediators leaked into the alveolar spaces is thought to be a major determinant of the respiratory failure in acute respiratory distress associated with lung injury (16,47). The surface-inhibitory activity of proteins such as albumin (8,48), fibrinogen (49), C-reactive protein (9,50), or lipases (51) toward surfactant has been well documented, as well as the deactivating effect of metabolites such as neutral lipids (46,52), FFAs (53), bile salts (54), heme derivatives (55), or lysophospholipids (33,53). Lung injury with different sources and to different extents is probably associated with particular complex and possibly multifactorial profiles of surfactant deactivation that have been only preliminarly characterized.…”

Section: Discussionmentioning

confidence: 99%

High-throughput evaluation of pulmonary surfactant adsorption and surface film formation

Ravasio

Cruz

Pérez‐Gil

et al. 2008

Journal of Lipid Research

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The assessment of new therapeutic strategies to cure surfactant-associated lung disorders would greatly benefit from assay systems allowing routine evaluations of surfactant functions. We present a method to measure surfactant adsorption kinetics into interfacial air-liquid interfaces based on fluorescence microplate readers. The principle of measurement is simple, robust, and reproducible: Wells of a microtiter plate contain an aqueous solution of a light-absorbing agent. Fluorescence is excited and collected from the top of the wells so that fluorescently labeled surfactant injected into the bulk can be detected only once adsorbed into the air-liquid interface. Mass transfer from the bulk to the interface is achieved by orbital shaking implemented in the plate reader instrument. The method has been tested and validated by using phospholipids or surfactants of different origins, by using albumin as surfactant inhibitor, and by comparison of results with Wilhelmy balance measurements. The method is suited for implementation in high-throughput screening routines for conditions affecting, or improving, surfactant film formation. In contrast to surface tension measurements, our method gives a direct readout of the amount of surfactant adsorbing into the interface, including the functionally important amount of material firmly associating with the interfacial film.-Ravasio, A., A. Cruz, J. Pérez-Gil, and T. Haller. High-throughput evaluation of pulmonary surfactant adsorption and surface film formation. J. Lipid Res. 2008Res. . 49: 2479Res. -2488

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“…blems. First, the supportive evidence is indirect, because it is derived largely from in vitro surface-tension data (7).…”

Section: Lungs) (C )mentioning

confidence: 99%

Micromechanics of Alveolar Edema

Perlman

Lederer²,

Bhattacharya³

2011

Am J Respir Cell Mol Biol

103

106

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The decrease of lung compliance in pulmonary edema underlies ventilator-induced lung injury. However, the cause of the decrease in compliance is unknown. We tested the hypothesis that in pulmonary edema, the mechanical effects of liquid-filled alveoli increase tissue stress in adjacent air-filled alveoli. By micropuncture of isolated, perfused rat lungs, we established a single-alveolus model of pulmonary edema that we imaged using confocal microscopy. In this model, we viewed a liquid-filled alveolus together with its airfilled neighbor at different transpulmonary pressures, both before and after liquid-filling. Instilling liquid in an alveolus caused alveolar shrinkage. As a result, the interalveolar septum was stretched, causing the neighboring air-filled alveolus to bulge. Thus, the airfilled alveolus was overexpanded by virtue of its adjacency to a liquid-filled alveolus. Confocal microscopy at different depths of the liquid-filled alveolus revealed a meniscus. Lung inflation to neartotal lung capacity (TLC) demonstrated decreased compliance of the air-filled but not liquid-filled alveolus. However, at near TLC, the airfilled alveolus was larger than it was in the pre-edematous control tissue. In pulmonary edema, liquid-filled alveoli induce mechanical stress on air-filled alveoli, reducing the compliance of air-filled alveoli, and hence overall lung compliance. Because of increased mechanical stress, air-filled alveoli may be susceptible to overdistension injury during mechanical ventilation of the edematous lung.Keywords: alveolar edema; compliance; micromechanics; optical sectioning microscopy; fluorescence Pulmonary edema occurs in a stepwise manner such that in its initial stages, liquid-filled and air-filled alveoli lie juxtaposed to one another. This liquid-filling pattern is thought to result from the all-or-none mechanism (1), according to which the curved air-liquid interface in the alveolus establishes a transinterfacial force balance, governed according to the equation of Laplace. In this equation (P alv 2 P liq ) 5 2T/R, where P alv and P liq are pressures in the alveolar air and liquid, respectively, T is the airliquid interfacial surface tension, and R is the interfacial radius. The alveolar entry of edema liquid at constant P alv is thought to increase T, thereby reducing P liq and further promoting liquid entry from the interstitium. This process continues until the interfacial curvature, and thus the pressure difference across the interface, is abolished. Importantly, these force considerations may be sufficiently localized that a single alveolus fills with fluid, while its immediate neighbor remains air-filled.Although the all-or-none mechanism provides an explanation of how single alveoli become liquid-filled during the initiating phase of pulmonary edema, there is little understanding of how the juxtaposition of air-filled and liquid-filled alveoli affects lung mechanics. The critical questions involve whether meniscus formation occurs in the liquid-filled alveolus (1, 2), and whether a...

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A Concentration-Dependent Mechanism by which Serum Albumin Inactivates Replacement Lung Surfactants

Cited by 80 publications

References 34 publications

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

High-throughput evaluation of pulmonary surfactant adsorption and surface film formation

Micromechanics of Alveolar Edema

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