Lipopeptides in the triggering of erythrocyte cell membrane scrambling

Sepsis is paralleled by anemia, an effect partially resulting from eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Pathogen-induced eryptosis may partially result from interaction of bacterial cell wall components such as lipoproteins with the erythrocyte cell membrane. The present study explored, whether the synthetic lipopeptide Pam3CSK4 mimicking the acylated amino terminus of bacterial lipoproteins triggers eryptosis. According to annexin-V-binding in FACS analysis, Pam3CSK4 (1 microg/ml) stimulated phosphatidylserine exposure, an effect significantly blunted in the nominal absence of Ca(2+). According to Fluo3 fluorescence, Pam3CSK4 increased cytosolic Ca(2+) activity and moderately stimulated erythrocytic ceramide formation, both major triggers of eryptosis. In conclusion, bacterial lipoproteins participate in the stimulation of erythrocyte cell membrane scrambling by bacterial cell wall components. Thus, lipoprotein-dependent suicidal erythrocyte death may contribute to the pleotropic effects of sepsis.