title: Stimulated Suicidal Erythrocyte Death in Arteritis.
abstract: OBJECTIVE
  Arteritis is an inflammatory disease of the vascular wall leading to ischemia and vascular occlusion. Complications of arteritis include anemia, which could, at least in theory, result from suicidal erythrocyte death or eryptosis, which is characterized by erythrocyte shrinkage and phosphatidylserine (PS) exposure at the erythrocyte surface. Cellular mechanisms involved in the stimulation of eryptosis include increased cytosolic Ca2+-concentration ([Ca2+]i), oxidative stress and ceramide formation. The present study explored whether and how arteritis influences eryptosis.
  
  
  METHODS
  Blood was drawn from patients suffering from arteritis (n=17) and from healthy volunteers (n=21). PS exposure was estimated from annexin V-binding, erythrocyte volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) from DCFDA fluorescence and ceramide abundance from FITC-conjugated antibody binding in flow cytometry. The patients suffered from anemia despite 2.8±0.4% reticulocytes.
  
  
  RESULTS
  The percentage of PS-exposing erythrocytes was significantly higher in patients (1.1±0.1%) than in healthy volunteers (0.3±0.1%). The increase in PS exposure was paralleled by increase in oxidative stress and [Ca2+]i but not by significant changes of ceramide abundance. Erythrocyte PS exposure and ROS production were significantly enhanced in erythrocytes exposed to patient plasma as compared to exposure to plasma from healthy volunteers.
  
  
  CONCLUSIONS
  Arteritis is associated with enhanced eryptosis due to increased [Ca2+]i and oxidative stress. The eryptosis contributes to or even accounts for the anemia in those patients. As eryptotic erythrocytes adhere to endothelial cells of the vascular wall, they could impede microcirculation and thus contribute to vascular occlusion.
authors.affiliation: Department of Cardiology, Vascular Medicine and Physiology, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany.
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Kempe-Teufel
authors.forename: Sabina
authors.initials: S
authors.lastname: Honisch
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.forename: Elko
authors.initials: E
authors.lastname: Randrianarisoa
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Jörg
authors.initials: J
authors.lastname: Henes
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood* / Q000150:complications / Q000473:pathology; D000814:Aniline Compounds; D017304:Annexin A5; D001167:Arteritis / Q000097:blood* / Q000150:complications / Q000473:pathology; D002118:Calcium / Q000097:blood*; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood; D000072817:Eryptosis; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010718:Phosphatidylserines / Q000097:blood*; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000097:blood; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D017304:Annexin A5; D002518:Ceramides; D005452:Fluoresceins; D005456:Fluorescent Dyes; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D014966:Xanthenes; C029569:diacetyldichlorofluorescein; C059715:Fluo-3; D002118:Calcium