Interaction of serum proteins with lung endothelial glycocalyx: its effect on endothelial permeability

Schneeberger, Eveline E.; Hamelin, Marie‐Hélène

doi:10.1152/ajpheart.1984.247.2.h206

Cited by 71 publications

(66 citation statements)

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“…As previously mentioned, the albumin from the culture media is adsorbed throughout the expanse of the glycocalyx, which gives it its full thickness. 43 From confocal measurements of BSA immunofluorescence, the total glycocalyx in healthy conditions was found to have a thickness of 3.2±0.2 µm and cover 75.2%±4.0% (Figure 2) of the EC layer surface. Upon immunostaining and measurement of the HS subcomponent of the glycocalyx, it was found to be 1.8±0.2 µm thick and to cover 75.2%±10.6% of the RFPEC surface ( Figure 3).…”

Section: Resultsmentioning

confidence: 97%

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Cheng¹,

Kumar²,

Sridhar³

et al. 2016

IJN

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Cardiovascular diseases are facilitated by endothelial cell (EC) dysfunction and coincide with EC glycocalyx coat shedding. These diseases may be prevented by delivering medications to affected vascular regions using circulating nanoparticle (NP) drug carriers. The objective of the present study was to observe how the delivery of 10 nm polyethylene glycol-coated gold NPs (PEG-AuNP) to ECs is impacted by glycocalyx structure on the EC surface. Rat fat pad endothelial cells were chosen for their robust glycocalyx, verified by fluorescent immunolabeling of adsorbed albumin and integrated heparan sulfate (HS) chains. Confocal fluorescent imaging revealed a ~3 µm thick glycocalyx layer, covering 75% of the ECs and containing abundant HS. This healthy glycocalyx hindered the uptake of PEG-AuNP as expected because glycocalyx pores are typically 7 nm wide. Additional glycocalyx models tested included: a collapsed glycocalyx obtained by culturing cells in reduced protein media, a degraded glycocalyx obtained by applying heparinase III enzyme to specifically cleave HS, and a recovered glycocalyx obtained by supplementing exogenous HS into the media after enzyme degradation. The collapsed glycocalyx waŝ2 µm thick with unchanged EC coverage and sustained HS content. The degraded glycocalyx showed similar changes in EC thickness and coverage but its HS thickness was reduced to 0.7 µm and spanned only 10% of the original EC surface. Both dysfunctional models retained six- to sevenfold more PEG-AuNP compared to the healthy glycocalyx. The collapsed glycocalyx permitted NPs to cross the glycocalyx into intracellular spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2 µm and 44% coverage of the ECs, but it was able to reverse the NP uptake back to baseline levels. In summary, this study showed that the glycocalyx structure is critical for NP uptake by ECs and may serve as a passive pathway for delivering NPs to dysfunctional ECs.

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Section: Resultsmentioning

confidence: 97%

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Cheng¹,

Kumar²,

Sridhar³

et al. 2016

IJN

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“…Such albumin binding to the endothelial surface has been demonstrated (39,40,48). Furthermore, the removal of albumin from the perfusate was shown to increase the loading of macromolecules into vesicles on the luminal surface of endothelium (33,38). Giantsos and colleagues (15) have described the development of cationized polymers that bind to the endothelial surface and reduce the permeability of endothelial monolayers.…”

Section: Discussionmentioning

confidence: 98%

Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect

Adamson

Clark

Radeva

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Adamson RH, Clark JF, Radeva M, Kheirolomoom A, Ferrara KW, Curry FE. Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect. Am J Physiol Heart Circ Physiol 306: H1011-H1017, 2014. First published February 15, 2014 doi:10.1152/ajpheart.00829.2013.-Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (P s)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with P s when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 Ϯ 46 nM) was near the normal plasma value at 37°C and established a stable baseline P s (0.9 Ϯ 0.4 ϫ 10 Ϫ6 cm/s). Ringer solution perfusate contained 52 Ϯ 8 nM S1P and increased P s more than 10-fold (16.1 Ϯ 3.9 ϫ 10 Ϫ6 cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium. albumin; endothelium; permeability; sphingosine-1-phosphate; vascular WE AND OTHERS have demonstrated that red blood cells (RBCs) are an important source of the plasma phospholipid sphingosine-1-phosphate (S1P), which acts continuously to maintain normal vascular permeability (7,9,24,34,43,50). The aim of the present experiments was to investigate the mechanisms that control the delivery of S1P from RBCs to the endothelium in intact microvessels. Our specific focus was the action of albumin as a carrier of S1P and as a modulator of vascular permeability. It has been known for many decades that the presence of albumin in vascular perfusates stabilizes the endothelial barrier (13,14,18,23,25,28,46). Removal of plasma proteins from perfusates increases vascular permeability and results in loss of the endothelial glycocalyx (11,29,32,33).The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic bindin...

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“…The raised permeability associated with removal of protein can be readily and completely reversed by perfusion with albumin containing solutions (Mason et al, 1979;. Furthermore, there is strong evidence that serum albumin binds reversibly to the luminal surface of the endothelium (Schneeberger & Hamelin, 1984;Schnitzer et al, 1988), and since its removal from this site is associated with the permeability increase, it has been proposed that the ultrafilter of capillary walls and a major component of the hydraulic resistance of the pathways through them, reside in a lattice-like structure formed by the interaction of plasma proteins with the luminal endothelial glycocalyx (Curry & Michel, 1980;see Michel, 1988, for review). Thus when Blumberg et al (1989) observed a reduction of permeability without the disappearance of the endothelial gaps, they suggested that HR might reduce the permeability of an extracellular barrier such as the glycocalyx.…”

Section: Preparationmentioning

confidence: 99%

Effects of hydroxyethylrutosides on the permeability of microvessels in the frog mesentery

Kendall

Towart²,

Michel

1993

British J Pharmacology

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1 We have investigated the effects of a standardised mixture of hydroxyethylrutosides (HR, Venoruton), a mixture of five of its main components (M) and each of the five components separately 7, 7,3', 5,7,3', upon the permeability of single perfused capillaries and venules in the mesenteries of pithed frogs.2 In each experiment, the hydraulic permeability (Lp) of a single perfused microvessel and the effective osmotic pressure (aAic) exerted by macromolecules across its walls were estimated by a microcclusion technique, first during control perfusion and then in the presence of a known concentration of test substance.3 HR, M and 7,4'-di-HR reduced Lp in a similar concentration-dependent manner over the range of 1 tLg ml-' to 1 mg ml-' (maximum reduction was to 40% of control Lp at 1 mg ml-'). At perfusate concentrations greater than 1 mg ml-', these substances reduced Lp to a lesser extent. While the four other test substances reduced Lp significantly when their perfusate concentrations equalled or exceeded 100 ig ml-1, they were all less potent than 7,4'-di-HR. 4 The reduction in Lp induced by the mixture of flavonoids was only slightly reversed by subsequent perfusion with flavonoid-free solutions. 5 When permeability was increased by perfusing with protein-free solutions, both HR and 7,4'-di-HR reduced and then reversed the increase in Lp in a concentration-dependent manner over the range of 1 jg ml' to 100 yg ml-'. None of the other component flavonoids was effective in restoring Lp under these conditions.

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Interaction of serum proteins with lung endothelial glycocalyx: its effect on endothelial permeability

Cited by 71 publications

References 0 publications

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect

Effects of hydroxyethylrutosides on the permeability of microvessels in the frog mesentery

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