title: Retinoic acid induced suicidal erythrocyte death.
abstract: Vitamin A and retinoic acid have previously been shown to confer some protection against a severe course of malaria by fostering the phagocytosis of parasitized erythrocytes. Phagocytosis of erythrocytes is stimulated by phosphatidylserine exposure at the cell surface. The present study has thus been performed to explore the effect of retinoic acid and the specific retinoic acid receptor (RAR) agonist 4-(E-2-[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl]-1-propenyl) benzoic acid (TTNPB) on erythrocyte annexin V binding, which reflects phosphatidylserine exposure at the cell surface. A 24 hours exposure to either, retinoic acid (3 microM) or TTNPB (3 microM), indeed significantly increased annexin binding, an effect paralleled by decrease of forward scatter reflecting cell shrinkage. According to Fluo3 fluorescence, exposure to either, retinoic acid (10 microM, 24 hours) or TTNPB (10 microM, 6 hours), significantly increased cytosolic Ca(2+)-activity, a known trigger of phosphatidylserine exposure. Infection of erythrocytes with Plasmodium falciparum increased phosphatidylserine exposure, an effect increased in the presence of TTNPB. In conclusion, retinoid acid and TTNPB trigger phosphatididylserine exposure and cell shrinkage of erythrocytes, typical features of suicidal erythrocyte death or eryptosis. The eryptosis could participate in the accelerated clearance of parasitized erythrocytes from circulating blood following treatment with retinoids.
authors.affiliation: Department of Physiology, University of Tuebingen, Tubingen, Germany.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Niemoeller
authors.forename: Michael
authors.initials: M
authors.lastname: Foller
authors.forename: Camelia
authors.initials: C
authors.lastname: Lang
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D017302:Annexins / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology; D005453:Fluorescence; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D010963:Plasmodium falciparum; D011485:Protein Binding / Q000187:drug effects; D012176:Retinoids / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D017302:Annexins; D001565:Benzoates; D012176:Retinoids; D014966:Xanthenes; C059715:Fluo-3; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; D002154:Calpain; D020169:Caspases; D005978:Glutathione