title: Regulation of phosphatidylserine exposure in red blood cells.
abstract: The exposure of phosphatidylserine (PS) on the outer membrane leaflet of red blood cells (RBCs) serves as a signal for eryptosis, a mechanism for the RBC clearance from blood circulation. The process of PS exposure was investigated as function of the intracellular Ca(2+) content and the activation of PKCα in human and sheep RBCs. Cells were treated with lysophosphatidic acid (LPA), 4-bromo-A23187, or phorbol-12 myristate-13 acetate (PMA) and analysed by flow cytometry, single cell fluorescence video imaging, or confocal microscopy. For human RBCs, no clear correlation existed between the number of cells with an elevated Ca(2+) content and PS exposure. Results are explained by three different mechanisms responsible for the PS exposure in human RBCs: (i) Ca(2+)-stimulated scramblase activation (and flippase inhibition) by LPA, 4-bromo-A23187, and PMA; (ii) PKC activation by LPA and PMA; and (iii) enhanced lipid flop caused by LPA. In sheep RBCs, only the latter mechanism occurs suggesting absence of scramblase activity.
authors.affiliation: Faculty of Natural and Technical Sciences III, Saarland University, Saarbruecken, Germany.
authors.forename: Duc Bach
authors.initials: DB
authors.lastname: Nguyen
authors.forename: Lisa
authors.initials: L
authors.lastname: Wagner-Britz
authors.forename: Sara
authors.initials: S
authors.lastname: Maia
authors.forename: Patrick
authors.initials: P
authors.lastname: Steffen
authors.forename: Christian
authors.initials: C
authors.lastname: Wagner
authors.forename: Lars
authors.initials: L
authors.lastname: Kaestner
authors.forename: Ingolf
authors.initials: I
authors.lastname: Bernhardt
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism; D012756:Sheep
chemical_list: D008246:Lysophospholipids; D010703:Phorbol Esters; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D000001:Calcimycin; C033170:4-bromo-A-23187; C032974:12-O-retinoylphorbol-13-acetate; D051571:Protein Kinase C-alpha; C032881:lysophosphatidic acid; D002118:Calcium