Enhanced adherence of human uremic erythrocytes to vascular endothelium: Role of phosphatidylserine exposure

Bonomini, Mario; Sirolli, Vittorio; Gizzi, F.; Stante, Silvio Di; Grilli, Alfredo; Felaco, Mario

doi:10.1111/j.1523-1755.2002.kid560.x

Cited by 54 publications

(39 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have shown that RBCs from patients on hemodialysis have an increased propensity to adhere to human endothelial cell monolayers, possibly via a direct interaction between PS exposed on the external leaflet of the erythrocyte plasma membrane and thrombospondin in the subendothelial matrix (82). Interestingly, we observed that adhesion of RBCs from uremic patients to the vascular endothelium may modulate NO release by endothelial cultures (83), as previously demonstrated for sickle RBC (84).…”

Section: Rbc-endothelial Cell Interactionsupporting

confidence: 65%

Erythrocyte Alterations and Increased Cardiovascular Risk in Chronic Renal Failure

et al. 2017

Self Cite

View full text Add to dashboard Cite

Patients suffering from chronic renal failure have a higher burden of cardiovascular events, which increases in a dose-dependent fashion as renal function worsens. Increased cardiovascular risk in these patients is thought to be mediated by the simultaneous presence of both traditional and non-traditional cardiovascular risk factors, the latter being associated with renal impairment. Red blood cells are usually considered as carries of nutrients for tissues and respiratory gases, less so as compartments essential to vascular integrity. However, erythrocyte number, size, and integrity seem to severely affect cardiovascular morbidity and mortality as established in recent clinical studies with large patient cohorts. In particular, the role of red blood cells in chronic renal failure tends only to be considered exclusively in relation to a change in their number. However, these cells in the uremic milieu are prone to many alterations, which may adversely affect the cardiovascular system. In this review, we highlight the main qualitative erythrocyte alterations that may have a pathophysiologic role in the elevated cardiovascular risk of chronic renal failure.

show abstract

Section: Rbc-endothelial Cell Interactionsupporting

confidence: 65%

Erythrocyte Alterations and Increased Cardiovascular Risk in Chronic Renal Failure

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…The HUVEC utilized in the present study express several adhesion molecules including integrins ␣ v (e.g., ␣ v ␤ 3 , or ␣ v ␤ 5 ) and ␤ 1 , E-and P-selectins, laminin ␣ 5 , vWF, and the adhesion molecules ICAM-1, PECAM-1, or VCAM-1 (3,8) and are thus widely used as model cells for adhesion to the vascular wall (3,8,9,54). Similar to what was shown in earlier studies (57) blocking phosphatidylserines or neutralizing CXCL16 by antibodies decreased but did not fully abrogate adhesion.…”

Section: Discussionmentioning

confidence: 99%

Sphingomyelinase-induced adhesion of eryptotic erythrocytes to endothelial cells

Abed

Towhid

Mia

et al. 2012

American Journal of Physiology-Cell Physiology

141

101

View full text Add to dashboard Cite

Eryptosis, the suicidal erythrocyte death, leads to cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes adhere to the vascular wall by binding of phosphatidylserine to the CXC chemokine ligand 16 (CXCL16). Stimulators of eryptosis include increased cytosolic Ca 2ϩ activity, energy depletion, and activation of ceramide-producing sphingomyelinase. The present study explored whether sphingomyelinase triggers erythrocyte adhesion to endothelial cells. To this end, human erythrocytes were exposed for 6 h to bacterial sphingomyelinase (1-10 mU/ml) and phosphatidylserine exposure was estimated from fluorescent annexin-V-binding, cell volume from forward scatter in FACS-analysis, erythrocyte adhesion to human umbilical vein endothelial cells (HUVEC) from trapping of labeled erythrocytes in a flow chamber under flow conditions at arterial shear rates, and CXCL16 protein abundance utilizing Western blotting and FACS analysis of fluorescent antibody binding. As a result, sphingomyelinase (Ն1 mU/ml) triggered cell shrinkage, phosphatidylserine exposure and erythrocyte adhesion to HUVEC, effects blunted by Ca 2ϩ removal. Adhesion was significantly blunted by phosphatidylserine-coating annexin-V (5 l/ml), following addition of neutralizing antibodies against endothelial CXCL16 (4 g/ml) and following silencing of the CXCL16 gene with small interfering RNA. Pretreatment of HUVEC with sphingomyelinase upregulated CXCL16 protein abundance. Six hours pretreatment of HUVEC with sphingomyelinase (10 mU/ml) or C6-ceramide (50 M) augmented erythrocyte adhesion following a 30-min treatment with Ca 2ϩ ionophore ionomycin (1 M) or following energy depletion by 48-h glucose removal. Thus exposure to sphingomyelinase or C6-ceramide triggers eryptosis followed by phosphatidylserine-and CXCL16-sensitive adhesion of eryptotic erythrocytes to HUVEC.

show abstract

“…HUVEC are a widely used model for cellular interactions with the vascular endothelium under flow conditions with different shear rates representing different size of arteries (3,9,10,57). They were shown to express different adhesion receptors including ␣ v integrins (e.g., ␣ v ␤ 3 or ␣ v ␤ 5 ), ␤ 1 integrins, E-and P-selectins, laminin ␣ 5 , von Willebrand factor, and the adhesion molecules ICAM-1, PECAM-1, or VCAM-1 (3,9).…”

Section: Discussionmentioning

confidence: 99%

Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX

Borst

Abed²,

Alesutan³

et al. 2012

American Journal of Physiology-Cell Physiology

222

215

View full text Add to dashboard Cite

Suicidal death of erythrocytes, or eryptosis, is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Eryptosis is triggered by increase of cytosolic Ca2+activity, which may result from treatment with the Ca2+ionophore ionomycin or from energy depletion by removal of glucose. The present study tested the hypothesis that phosphatidylserine exposure at the erythrocyte surface fosters adherence to endothelial cells of the vascular wall under flow conditions at arterial shear rates and that binding of eryptotic cells to endothelial cells is mediated by the transmembrane CXC chemokine ligand 16 (CXCL16). To this end, human erythrocytes were exposed to energy depletion (for 48 h) or treated with the Ca2+ionophore ionomycin (1 μM for 30 min). Phosphatidylserine exposure was quantified utilizing annexin-V binding, cell volume was estimated from forward scatter in FACS analysis, and erythrocyte adhesion to human vascular endothelial cells (HUVEC) was determined in a flow chamber model. As a result, both, ionomycin and glucose depletion, triggered eryptosis and enhanced the percentage of erythrocytes adhering to HUVEC under flow conditions at arterial shear rates. The adhesion was significantly blunted in the presence of erythrocyte phosphatidylserine-coating annexin-V (5 μl/ml), of a neutralizing antibody against endothelial CXCL16 (4 μg/ml), and following silencing of endothelial CXCL16 with small interfering RNA. The present observations demonstrate that eryptotic erythrocytes adhere to endothelial cells of the vascular wall in part by interaction of phosphatidylserine exposed at the erythrocyte surface with endothelial CXCL16.

show abstract

Enhanced adherence of human uremic erythrocytes to vascular endothelium: Role of phosphatidylserine exposure

Abstract: These findings suggest that PS externalization may promote increased uremic erythrocyte adhesion to endothelium, possibly via a direct interaction with matrix thrombospondin.

Cited by 54 publications

References 34 publications

Erythrocyte Alterations and Increased Cardiovascular Risk in Chronic Renal Failure

Erythrocyte Alterations and Increased Cardiovascular Risk in Chronic Renal Failure

Sphingomyelinase-induced adhesion of eryptotic erythrocytes to endothelial cells

Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX

Contact Info

Product

Resources

About