Stimulation of eryptosis by anti-A IgG antibodies.
Anti-A IgG antibodies have previously been shown to stimulate Ca(2+) entry into red blood cells. Increased cytosolic free Ca(2+) concentration is known to trigger eryptosis, i.e. suicidal erythrocyte death, characterized by exposure of phosphatidylserine at the erythrocyte surface. As macrophages are equipped with phosphatidylserine receptors, they bind, engulf and degrade phosphatidylserine exposing cells. The present experiments have been performed to explore whether anti-A IgGs trigger phosphatidylserine exposure of erythrocytes. Phosphatidylserine exposure was estimated from annexin-V binding as determined in FACS analysis. Exposure to anti-A IgGs (0.5 microg/ml) indeed significantly increased annexin-V binding in erythrocytes with blood group A, but not in erythrocytes with blood group 0. According to Fluo3 fluorescence, anti-A IgGs increased cytosolic Ca(2+) concentration. Whole cell patch clamp recordings revealed the activation of a Ca(2+)-permeable cation channel following treatment with anti-A-IgGs. Annexin-V binding following anti-A IgG exposure was blunted by Ca(2+) removal while anti-A IgG-stimulated cation channel activity was not dependent on extracellular Ca(2+). Osmotic shock (exposure of erythrocytes to 850 mOsm) increased annexin binding, an effect further enhanced by exposure to anti-A IgGs. In conclusion, anti-A IgGs activate erythrocyte cation channels leading to Ca(2+) entry and subsequent erythrocyte cell membrane scrambling. The effect most likely contributes to the elimination of erythrocytes following an immune reaction against the A antigen.
Attanasio
Philipp
P
Department of Physiology, University of Tübingen, Tübingen, Germany.
Shumilina
Ekaterina
E
Hermle
Tobias
T
Kiedaisch
Valentin
V
Lang
Philipp A
PA
Huber
Stephan M
SM
Wieder
Thomas
T
Lang
Florian
F
D017209:Apoptosis / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D009997:Osmotic Pressure / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010718:Phosphatidylserines / Q000494:pharmacology
D002518:Ceramides; D007074:Immunoglobulin G; D010718:Phosphatidylserines; D002118:Calcium