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Regulation of Phosphatidylserine Exposure in Red Blood Cells

2011; Karger Publishers; Volume: 28; Issue: 5 Linguagem: Inglês

10.1159/000335798

1421-9778

Duc Bach Nguyen, Lisa Wagner-Britz, Sara Maia, Patrick R. Steffen, Christian Wagner, Lars Kaestner, Ingolf Bernhardt,

Blood properties and coagulation

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 Ca2+ 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 Ca2+ content and PS exposure. Results are explained by three different mechanisms responsible for the PS exposure in human RBCs: (i) Ca2+-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.