Role of glycocalyx in leukocyte-endothelial cell adhesion

Mulivor, Aaron W.; Lipowsky, Herbert H.

doi:10.1152/ajpheart.00117.2002

Cited by 306 publications

(310 citation statements)

References 27 publications

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“…46,[65][66][67] Of note, our intravital microscopy data are registered in postcapillary venules, which are slightly broader and downstream of the narrowest capillaries, where a few adhering leukocytes can restrain flow pattern in a way as observed directly in conditions of reduced glycocalyx (http://www.youtube.com/ watch?feature=player_embedded&v=6wHBninEwHA). All these arguments together suggest that the disturbed leukocyte-endothelium crosstalk as visually observed by us on the one hand and the biochemical and morphologic findings that conform with glycocalyx changes on the other hand are interrelated.…”

Section: Discussionmentioning

confidence: 99%

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Pletinck

Glorieux

Schepers

et al. 2013

Journal of the American Society of Nephrology

100

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Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.

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Section: Discussionmentioning

confidence: 99%

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Pletinck

Glorieux

Schepers

et al. 2013

Journal of the American Society of Nephrology

100

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“…By importing the values of B and C max from the experiments of Mulivor et al, we regress k f and k r to fit the expression in eq 3 to the experimental data in ref 13 , both in the presence of and in the absence of the glycocalyx (see Figure 2 and Appendix A2). Using the inferred values of k f and k r , we compute the equilibrium constant K in the presence and in the absence of glycocalyx.…”

Section: Parameter Estimationmentioning

confidence: 99%

The Role of Glycocalyx in Nanocarrier-Cell Adhesion Investigated Using a Thermodynamic Model and Monte Carlo Simulations

Agrawal

Radhakrishnan

2007

J. Phys. Chem. C

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We present an equilibrium model for quantifying the effect of glycocalyx in mediating the interaction of functionalized nanocarriers with endothelial cells. In this model, nanocarrier adhesion is governed by the interplay between three physical parameters, namely, glycocalyx resistance, flexural rigidity of receptors, and receptor-ligand bond stiffness. We describe a procedure to rationally determine the values of these crucial parameters based on several independent (single molecule and cell-based) characterizing experiments. Using our model and independent derivation of the parameter values in conjunction with Monte Carlo simulations, we describe the binding of nanocarriers to endothelial cells at equilibrium. We show that we can quantitatively reproduce the experimental binding affinities with zero fitting to binding data. Additionally, our simulations provide quantitative descriptions for the multivalency in nanocarrier binding, as well as for the degree of clustering of antigens. Our study identifies two interesting parameters: glycocalyx resistance and antigen flexural rigidity, both of which reduce binding of nanocarriers and alter the sensitivity of the nanocarrier binding constant to changes in temperature. Collectively, our model, parameter estimations, simulations, and sensitivity analyses help provide unified molecular and energetic analyses of the nanocarrier binding process.

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“…The possible roles of the endothelial glycocalyx (EG) in this regulation as a molecular sieve, as a barrier and modulator of interactions between blood cells and ECs, and as a mechanotransducer of fluid shear stress have been studied more recently (4)(5)(6)(7). Relatively little is known about the specific proteins in the EG, although hyaluronan, chondroitin, and heparan sulfate play a significant role in its assembly (8,9).…”

mentioning

confidence: 99%

The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper-car” model

Thi

Tarbell

Weinbaum

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

289

308

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We propose a conceptual model for the cytoskeletal organization of endothelial cells (ECs) based on a major dichotomy in structure and function at basal and apical aspects of the cells. Intracellular distributions of filamentous actin (F-actin), vinculin, paxillin, ZO-1, and Cx43 were analyzed from confocal micrographs of rat fat-pad ECs after 5 h of shear stress. With intact glycocalyx, there was severe disruption of the dense peripheral actin bands (DPABs) and migration of vinculin to cell borders under a uniform shear stress (10.5 dyne͞cm 2 ; 1 dyne ‫؍‬ 10 N). This behavior was augmented in corner flow regions of the flow chamber where high shear stress gradients were present. In striking contrast, no such reorganization was observed if the glycocalyx was compromised. These results are explained in terms of a ''bumper-car'' model, in which the actin cortical web and DPAB are only loosely connected to basal attachment sites, allowing for two distinct cellular signaling pathways in response to fluid shear stress, one transmitted by glycocalyx core proteins as a torque that acts on the actin cortical web (ACW) and DPAB, and the other emanating from focal adhesions and stress fibers at the basal and apical membranes of the cell. mechanotransduction ͉ actin cortical web ͉ dense peripheral actin band H emodynamic shearing stresses on endothelial cells (ECs) are widely recognized as playing a vital role in the regulation of vessel wall remodeling, cellular signaling, mass transport, red and white cell interaction, and atherogenesis (1-3). The possible roles of the endothelial glycocalyx (EG) in this regulation as a molecular sieve, as a barrier and modulator of interactions between blood cells and ECs, and as a mechanotransducer of fluid shear stress have been studied more recently (4-7). Relatively little is known about the specific proteins in the EG, although hyaluronan, chondroitin, and heparan sulfate play a significant role in its assembly (8, 9). In the early 1990s, investigators first observed that the shear-induced dilation of small arteries was abolished when sialic acids were removed from the EG by neuraminidase (10). Florian et al. (11) recently verified the presence of heparan sulfate proteoglycan (HSPG) in the glycocalyx of cultured bovine aortic ECs and demonstrated that partial removal of HSPG with heparinase completely blocked shear-induced NO release. A puzzling and still not understood consequence of EG degradation was the observation that shear-induced NO production was greatly inhibited without apparent effect on shear-dependent vasodilation due to prostaglandin I 2 release (12). Squire et al. (13) showed that the ultrastructural organization of the EG was quasiperiodic, anchored to a geodesic-like scaffold of hexagonally arranged filamentous actin (F-actin) filaments forming an actin cortical web (ACW) (14) just beneath the plasmalemma. A fundamental question addressed in ref. 7 is how fluid shear stresses acting at the surface of the EG are transmitted to this ACW if there is essentially ...

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Role of glycocalyx in leukocyte-endothelial cell adhesion

Cited by 306 publications

References 27 publications

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

The Role of Glycocalyx in Nanocarrier-Cell Adhesion Investigated Using a Thermodynamic Model and Monte Carlo Simulations

The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper-car” model

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