Stimulation of erythrocyte ceramide formation by platelet-activating factor

Author:

Lang Philipp A.1,Kempe Daniela S.1,Tanneur Valerie1,Eisele Kerstin1,Klarl Barbara A.1,Myssina Svetlana1,Jendrossek Verena2,Ishii Satoshi3,Shimizu Takao3,Waidmann Marc4,Hessler Gabriele1,Huber Stephan M.1,Lang Florian1,Wieder Thomas1

Affiliation:

1. Department of Physiology, University of Tübingen, Germany

2. Department of Radiation Oncology, University of Tübingen, Germany

3. Department of Biochemistry and Molecular Biology, University of Tokyo, Japan

4. Department of Anesthesiology and Transfusion Medicine, University of Tübingen, Germany

Abstract

Osmotic erythrocyte shrinkage leads to activation of cation channels with subsequent Ca2+ entry and stimulates a sphingomyelinase with subsequent formation of ceramide. Ca2+ and ceramide then activate a scramblase leading to breakdown of phosphatidylserine asymmetry of the cell membrane. The mediators accounting for activation of erythrocyte sphingomyelinase and phosphatidylserine exposure remained elusive. The study demonstrates that platelet-activating factor (PAF) is released from erythrocytes upon hyperosmotic cell shrinkage. The experiments further disclose the presence of PAF receptors in erythrocytes and show that PAF stimulates the breakdown of sphingomyelin and the release of ceramide from erythrocytes at isotonic conditions. PAF further triggers cell shrinkage (decrease of forward scatter) and phosphatidylserine exposure (annexin binding) of erythrocytes. The stimulation of annexin-binding is blunted by a genetic knockout of PAF receptors, by the PAF receptor antagonist ABT491 or by inhibition of sphingomyelinase with urea. In conclusion, PAF activates an erythrocyte sphingomyelinase and the then formed ceramide leads to the activation of scramblase with subsequent phosphatidylserine exposure.

Publisher

The Company of Biologists

Subject

Cell Biology

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