Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte aging

Klei, Thomas R.; Back, Djuna Z. de; Asif, Paris Jabeen; Verkuijlen, Paul; Veldthuis, Martijn; Ligthart, Peter; Berghuis, Jeffrey; Clifford, Els; Beuger, Boukje M.; Berg, Timo K. van den; Zwieten, Rob van; Nemer, Wassim El; Bruggen, Robin van

doi:10.1182/bloodadvances.2017013094

Cited by 24 publications

(38 citation statements)

References 47 publications

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“…It has been suggested by others that during routine storage of RBCs, the adhesive capacity of RBCs increases over time due to RBC adhesion molecule activation. This may be an important novel mechanism to capture and clear senescent RBCs during homeostasis . Since freshly isolated RBCs do not adhere to laminin‐α5, we aimed to study RBC adhesion to laminin‐α5 after apheresis.…”

Section: Resultsmentioning

confidence: 99%

“…This may be an important novel mechanism to capture and clear senescent RBCs during homeostasis. 4 Since freshly isolated RBCs do not adhere to laminin-α5, we aimed to study RBC adhesion to laminin-α5 after apheresis. To study this, we used an assay to monitor RBC binding to laminin-α5 under physiologic flow conditions, using confocal microscopy.…”

Section: Rbc Binding To Laminin-α5 Remains Unaltered After Apheresismentioning

confidence: 99%

“…Furthermore, we also investigated RBC adhesion to an extracellular matrix component called laminin‐α5, since it is known that during RBC aging and or storage, the adhesion molecule Lu/BCAM becomes gradually activated due to loss of sialic acid on glycophorin‐C. Upon activation, Lu/BCAM engages a sialic acid–dependent interaction with laminin‐α5, which may be an important novel mechanism to capture and clear senescent RBCs during homeostasis.…”

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confidence: 99%

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Apheresis causes complement deposition on red blood cells (RBCs) and RBC antigen alterations, possibly inducing enhanced clearance

et al. 2018

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BACKGROUND Apheresis is increasingly being applied to collect cells or plasma, even allowing the collection of multiple blood components during one procedure. Although the quality of the cellular and plasma products that are obtained by apheresis have been extensively studied and shown to be of high quality, the impact of apheresis on the red blood cells (RBCs) that are returned to the donor has not been investigated. STUDY DESIGN AND METHODS The effect of the plasma‐ or plateletpheresis procedures by four different devices—MCS+ (Haemonetics), PCS2 (Haemonetics), Trima Accel (Terumo BCT), and Autopheresis‐C (Auto‐C, Fresenius Kabi)—on the RBCs that are returned to the donor was tested in a blinded, prospective trial in a cohort of 25 donors. RESULTS A rheologic analysis of donor RBCs before and after plasma‐ or plateletpheresis showed no differences in outcome. However, a strong increase in hemolysis was found in samples from the Trima Accel devices after plateletpheresis, compared to all other machines tested. Furthermore, an increase in complement deposition on RBCs was seen after all plasmapheresis procedures (MCS+, PCS2, and Auto‐C). Finally, a significant decrease in the expression of the complement‐regulating protein CD59 was seen in all postapheresis samples as well as a significant decrease of the adhesion molecule CD147. CONCLUSION The increase in complement deposition and the decrease in the expression of CD59 suggests that RBC clearance might be enhanced after return to the donor. Possible side effects due to an increase in hemolysis after Trima Accel plateletpheresis should be further investigated.

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Section: Resultsmentioning

confidence: 99%

Section: Rbc Binding To Laminin-α5 Remains Unaltered After Apheresismentioning

confidence: 99%

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confidence: 99%

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Apheresis causes complement deposition on red blood cells (RBCs) and RBC antigen alterations, possibly inducing enhanced clearance

et al. 2018

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“…The interaction of B-CAM/LU with laminin alpha 5 is inhibited when interacting in cis conformation, with GPC-derived sialic acid residues on the RBC. Upon loss of this interaction during aging, B-CAM/LU can interact, in trans, with sialic acid on laminin alpha 5 (Klei et al, 2018). In polycythemia vera, a myeloproliferative disorder characterized by a high occurrence of thrombosis, there is a correlation between the mutation of the janus kinase and phosphorylation of B-CAM/LU, which in turn initiates the interaction with endothelial laminin alpha 5 (Wautier et al, 2007; Wautier and Wautier, 2013).…”

Section: Plasma Proteins Mediated Interactionsmentioning

confidence: 99%

Red Blood Cells: Chasing Interactions

et al. 2019

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Human red blood cells (RBC) are highly differentiated cells that have lost all organelles and most intracellular machineries during their maturation process. RBC are fundamental for the nearly all basic physiologic dynamics and they are key cells in the body’s respiratory system by being responsible for the oxygen transport to all cells and tissues, and delivery of carbon dioxide to the lungs. With their flexible structure RBC are capable to deform in order to travel through all blood vessels including very small capillaries. Throughout their in average 120 days lifespan, human RBC travel in the bloodstream and come in contact with a broad range of different cell types. In fact, RBC are able to interact and communicate with endothelial cells (ECs), platelets, macrophages, and bacteria. Additionally, they are involved in the maintenance of thrombosis and hemostasis and play an important role in the immune response against pathogens. To clarify the mechanisms of interaction of RBC and these other cells both in health and disease as well as to highlight the role of important key players, we focused our interest on RBC membrane components such as ion channels, proteins, and phospholipids.

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“…These include vesiculation, and consequently loss of deformability, phosphatidylserine exposure, membrane desialylation, adenosine triphosphate depletion, and adhesion molecule activation. [1][2][3][4][5] Some of these are cause-and-effect processes, and others are seemingly unrelated. One of the best described phenomena that relate to erythrocyte senescence during the erythrocyte lifespan is the Gardos effect.…”

Section: Introductionmentioning

confidence: 99%

The Gardos effect drives erythrocyte senescence and leads to Lu/BCAM and CD44 adhesion molecule activation

et al. 2020

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Senescence of erythrocytes is characterized by a series of changes that precede their removal from the circulation, including loss of red cell hydration, membrane shedding, loss of deformability, phosphatidyl serine exposure, reduced membrane sialic acid content, and adhesion molecule activation. Little is known about the mechanisms that initiate these changes nor is it known whether they are interrelated. In this study, we show that Ca2+-dependent K+ efflux (the Gardos effect) drives erythrocyte senescence. We found that increased intracellular Ca2+ activates the Gardos channel, leading to shedding of glycophorin-C (GPC)–containing vesicles. This results in a loss of erythrocyte deformability but also in a marked loss of membrane sialic acid content. We found that GPC-derived sialic acid residues suppress activity of both Lutheran/basal cell adhesion molecule (Lu/BCAM) and CD44 by the formation of a complex on the erythrocyte membrane, and Gardos channel–mediated shedding of GPC results in Lu/BCAM and CD44 activation. This phenomenon was observed as erythrocytes aged and on erythrocytes that were otherwise prone to clearance from the circulation, such as sickle erythrocytes, erythrocytes stored for transfusion, or artificially dehydrated erythrocytes. These novel findings provide a unifying concept on erythrocyte senescence in health and disease through initiation of the Gardos effect.

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Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte aging

Cited by 24 publications

References 47 publications

Apheresis causes complement deposition on red blood cells (RBCs) and RBC antigen alterations, possibly inducing enhanced clearance

Apheresis causes complement deposition on red blood cells (RBCs) and RBC antigen alterations, possibly inducing enhanced clearance

Red Blood Cells: Chasing Interactions

The Gardos effect drives erythrocyte senescence and leads to Lu/BCAM and CD44 adhesion molecule activation

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