title: Dynamic adhesion of eryptotic erythrocytes to immobilized platelets via platelet phosphatidylserine receptors.
abstract: Glucose depletion of erythrocytes triggers suicidal erythrocyte death or eryptosis, which leads to cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes adhere to endothelial cells by a mechanism involving phosphatidylserine at the erythrocyte surface and CXCL16 as well as CD36 at the endothelial cell membrane. Nothing has hitherto been known about an interaction between eryptotic erythrocytes and platelets, the decisive cells in primary hemostasis and major players in thrombotic vascular occlusion. The present study thus explored whether and how glucose-depleted erythrocytes adhere to platelets. To this end, adhesion of phosphatidylserine-exposing erythrocytes to platelets under flow conditions was examined in a flow chamber model at arterial shear rates. Platelets were immobilized on collagen and further stimulated with adenosine diphosphate (ADP, 10 μM) or thrombin (0.1 U/ml). As a result, a 48-h glucose depletion triggered phosphatidylserine translocation to the erythrocyte surface and augmented the adhesion of erythrocytes to immobilized platelets, an effect significantly increased upon platelet stimulation. Adherence of erythrocytes to platelets was blunted by coating of erythrocytic phosphatidylserine with annexin V or by neutralization of platelet phosphatidylserine receptors CXCL16 and CD36 with respective antibodies. In conclusion, glucose-depleted erythrocytes adhere to platelets. The adhesive properties of platelets are augmented by platelet activation. Erythrocyte adhesion to immobilized platelets requires phosphatidylserine at the erythrocyte surface and CXCL16 as well as CD36 expression on platelets. Thus platelet-mediated erythrocyte adhesion may foster thromboocclusive complications in diseases with stimulated phosphatidylserine exposure of erythrocytes.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany;
authors.forename: Britta
authors.initials: B
authors.lastname: Walker
authors.forename: Syeda T
authors.initials: ST
authors.lastname: Towhid
authors.forename: Evi
authors.initials: E
authors.lastname: Schmid
authors.forename: Sascha M
authors.initials: SM
authors.lastname: Hoffmann
authors.forename: Majed
authors.initials: M
authors.lastname: Abed
authors.forename: Patrick
authors.initials: P
authors.lastname: Münzer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogel
authors.forename: Felix
authors.initials: F
authors.lastname: Neis
authors.forename: Sara
authors.initials: S
authors.lastname: Brucker
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism*; D010973:Platelet Adhesiveness; D011956:Receptors, Cell Surface / Q000378:metabolism; D051116:Receptors, Scavenger / Q000276:immunology / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism
chemical_list: D017304:Annexin A5; D018955:CD36 Antigens; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D010718:Phosphatidylserines; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; C408123:phosphatidylserine receptor; D000244:Adenosine Diphosphate; D013917:Thrombin; D005947:Glucose
keywords: CD36; CXCL16; dynamic adhesion; eryptosis; phosphatidylserine; platelets