Role of erythrocyte phosphatidylserine in sickle red cell–endothelial adhesion

Setty, B. N. Yamaja; Kulkarni, Surekha; Stuart, Marie J.

doi:10.1182/blood.v99.5.1564

Cited by 177 publications

(140 citation statements)

References 44 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Depletion affinity (A D ) can be written as [9]: (1) where Δ is the depletion layer thickness, Π the osmotic pressure and d the distance between the two surfaces. In case of so-called non-smooth, hairy surfaces such as the RBC with its glycocalyx, it is also necessary to consider the thickness δ of this attached layer and the penetration of the polymer into this layer.…”

Section: Discussionmentioning

confidence: 99%

“…During the past few decades, the adhesion of red blood cells (RBC) to other cells and to surfaces has been studied quite extensively due to at least two reasons: 1) Abnormal adhesiveness to other RBC and to endothelial cells has been linked to several diseases such as sickle cell anemia or diabetes mellitus [1,2]; 2) Red blood cells are relatively simple, easily obtainable cells thus making them logical choices to study the fundamentals of cell interactions in the circulation or with biomaterials. It is clear that various non-specific forces (e.g., electrostatic) and specific forces (e.g., cell adhesion molecules) govern RBC and other cell adhesion to cells or surfaces.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Depletion interactions in polymer solutions promote red blood cell adhesion to albumin-coated surfaces

Neu

Meiselman²

2006

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

The effects of concentration and molecular weight of neutral dextrans on the adhesion of human red blood cells (RBC) to albumin-coated glass have been investigated using a parallel-plate flow chamber. Results indicate that the adhesion is markedly increased in the presence of 70 kDa and 500 kDa dextran, with this increase reflected by both the number of cells adhering and the strength of the adhesion. This increased adhesiveness is attributed to reduced surface concentrations of the large polymers and hence attractive forces due to depletion interaction. Depletion interaction brings the adjacent surfaces closer, leading to an increased number of binding sites available to the cell and thus more efficient and stronger adhesion of single cells. Our results suggest that depletion might play a role in other specific cell-cell or cell-surface interactions via initiating close contacts to allow specific binding.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Depletion interactions in polymer solutions promote red blood cell adhesion to albumin-coated surfaces

Neu

Meiselman²

2006

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

show abstract

“…Occlusion of small blood vessels, tissue ischaemia and organ damage, as well as the chronic anaemia, are important features of the condition. Through its pro‐thrombotic and pro‐phagocytic activities, red cell phosphatidylserine (PS) may participate in vascular occlusion and destruction of red cells (Hebbel, 1991; Boas et al , 1998; Setty et al , 2002; Steffen et al , 2011). This paper concerns the mechanism of red cell PS exposure and the role of oxidative damage in sickle cell disease.…”

mentioning

confidence: 99%

Oxidative stress and phosphatidylserine exposure in red cells from patients with sickle cell anaemia

et al. 2018

View full text Add to dashboard Cite

SummaryPhosphatidylserine (PS) exposure increases as red cells age, and is an important signal for the removal of senescent cells from the circulation. PS exposure is elevated in red cells from sickle cell anaemia (SCA) patients and is thought to enhance haemolysis and vaso‐occlusion. Although precise conditions leading to its externalisation are unclear, high intracellular Ca2+ has been implicated. Red cells from SCA patients are also exposed to an increased oxidative challenge, and we postulated that this stimulates PS exposure, through increased Ca2+ levels. We tested four different ways of generating oxidative stress: hypoxanthine and xanthine oxidase, phenazine methosulphate, nitrite and tert‐butyl hydroperoxide, together with thiol modification with N‐ethylmaleimide (NEM), dithiothreitol and hypochlorous acid (HOCl), in red cells permeabilised to Ca2+ using bromo‐A23187. Unexpectedly, our findings showed that the four oxidants significantly reduced Ca2+‐induced PS exposure (by 40–60%) with no appreciable effect on Ca2+ affinity. By contrast, NEM markedly increased PS exposure (by about 400%) and slightly but significantly increased the affinity for Ca2+. Dithiothreitol modestly reduced PS exposure (by 25%) and HOCl had no effect. These findings emphasise the importance of thiol modification for PS exposure in sickle cells but suggest that increased oxidant stress alone is not important.

show abstract

“…5,6 The correlation between sickle cell adhesiveness and the severity of vascular occlusion 7 led to extensive studies of the molecular mechanisms of adhesion. These pathways recently have been reviewed [8][9][10][11][12] and are briefly described here. Sickle red cells express adhesion molecules including integrin ␣ 4 ␤ 1 , CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine, and integrin-associated protein.…”

Section: Introductionmentioning

confidence: 99%

Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin

Matsui

Varki

Embury

2002

Blood

115

110

View full text Add to dashboard Cite

The adhesion of sickle erythrocytes to vascular endothelium is important to the generation of vascular occlusion. Interactions between sickle cells and the endothelium use several cell adhesion molecules. We have reported that sickle cell adhesion to endothelial cells under static conditions involves P-selectin. Others have shown that sickle cell adhesion is decreased by unfractionated heparin, but the molecular target of this inhibition has not been defined. We postulated that the adhesion of sickle cells to P-selectin might be the pathway blocked by unfractionated heparin. In this report we demonstrate that the flow adherence of sickle cells to thrombin-treated human vascular endothelial cells also uses P-selectin and that this component of adhesion is inhibited by unfractionated heparin. We also demonstrate that sickle cells adhere to immobilized recombinant P-selectin under flow conditions. This adhesion too was inhibited by unfractionated heparin, in a concentration range that is clinically attainable. These findings and the general role of P-selectin in initiating adhesion of blood cells to the endothelium suggest that unfractionated heparin may be useful in preventing IntroductionVascular occlusion is responsible for much of the morbidity associated with sickle cell disease. 1,2 Although the underlying cause of sickle cell disease is a single nucleotide mutation that directs the production of an easily polymerized hemoglobin protein, 3,4 both the erythrocyte sickling caused by hemoglobin polymerization and the interactions between a proadhesive population of sickle cells and the vascular endothelium are essential to vascular occlusion. 5,6 The correlation between sickle cell adhesiveness and the severity of vascular occlusion 7 led to extensive studies of the molecular mechanisms of adhesion. These pathways recently have been reviewed [8][9][10][11][12] and are briefly described here. Sickle red cells express adhesion molecules including integrin ␣ 4 ␤ 1 , CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine, and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), CD36, and integrins. Activation of endothelial cells by specific agonists enhances adhesion by inducing the expression of cellular adhesion molecules and by causing cell contraction, which exposes extracellular matrix proteins, such as thrombospondin (TSP), laminin, and fibronectin. Bridging molecules from the plasma such as von Willebrand factor (VWF) and TSP also participate in certain of these adhesive interactions.Sickle cell adhesion has been studied under both static and flow conditions. 13 The relevance of both types of adhesion is suggested by in vivo observations of laminar, intermittent, and antegraderetrograde flow in the microvasculature of sickle cell subjects and sickle cell mouse models. [14][15][16] Initial events likely involve the adhesion of sickle erythrocytes to activated endothelial cells under ...

show abstract

Role of erythrocyte phosphatidylserine in sickle red cell–endothelial adhesion

Cited by 177 publications

References 44 publications

Depletion interactions in polymer solutions promote red blood cell adhesion to albumin-coated surfaces

Depletion interactions in polymer solutions promote red blood cell adhesion to albumin-coated surfaces

Oxidative stress and phosphatidylserine exposure in red cells from patients with sickle cell anaemia

Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin

Contact Info

Product

Resources

About