Adhesion of klotho-deficient eryptotic erythrocytes to endothelial cells

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AimSuicidal erythrocyte death or eryptosis is characterized by cell shrinkage and phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes may adhere to the vascular wall by binding of phosphatidylserine to endothelial CXC chemokine ligand 16 (CXCL16). Triggers of eryptosis include osmotic shock or energy depletion. Susceptibility to eryptosis is modified by Klotho, a protein with profound effect on ageing and lifespan. Klotho deficiency leads to accelerated ageing and early death. The percentage of eryptotic erythrocytes is significantly larger in klotho-deficient mice (klotho−/−) than in their wild-type littermates (klotho+/+). The present study explored whether the accelerated eryptosis of klotho-deficient mice is paralleled by enhanced adhesion.MethodsPhosphatidylserine-exposing erythrocytes were identified by measurement of annexin V binding and adhesion to human umbilical vein endothelial cells (HUVEC) from trapping of labelled erythrocytes in a flow chamber.ResultsAnnexin V binding was higher in klotho−/− erythrocytes than in klotho+/+ erythrocytes. Osmotic shock for 1 h (addition of 550 mM sucrose) and energy depletion (12-h glucose depletion) increased annexin V binding to values again significantly larger in klotho−/− erythrocytes than in klotho+/+ erythrocytes. klotho−/− erythrocytes were particularly sensitive to osmotic shock. Both osmotic shock and energy depletion enhanced erythrocyte adhesion, an effect again more pronounced in klotho−/− erythrocytes than in klotho+/+ erythrocytes. The adhesion was significantly decreased by coating of phospatidylserine with annexin V (5 μL mL1) or by coating of CXCL16 with neutralizing antibodies (4 μg mL1).Conclusionsklotho−/− erythrocytes are particularly sensitive to osmotic shock, and enhanced eryptosis of klotho−/− erythrocytes is paralleled by enhanced adhesion to endothelial CXCL16.

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