Suicidal erythrocyte death in sepsis.
Sequelae of sepsis include anemia which presumably results from accelerated clearance of erythrocytes from circulating blood. The underlying mechanisms, however, remained hitherto elusive. Most recent studies disclosed that increased cytosolic Ca2+ activity and ceramide both trigger suicidal erythrocyte death (i.e., eryptosis), which is characterized by lipid scrambling of the cell membrane leading to phosphatidylserine exposure at the erythrocyte surface. Phosphatidylserine exposing erythrocytes may adhere to vascular walls or may be engulfed by macrophages equipped with phosphatidylserine receptors. To explore whether sepsis leads to eryptosis, erythrocytes from healthy volunteers were exposed to plasma of patients suffering from sepsis, or to supernatants from sepsis producing pathogens. Then, phosphatidylserine exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3 fluorescence), and ceramide formation (anti-ceramide antibody) were determined by flow cytometry. Challenge of erythrocytes with plasma from the patients but not with plasma from healthy individuals triggered annexin V binding. The effect of patient plasma on erythrocyte annexin V binding was paralleled by formation of ceramide and a significant increase of cytosolic Ca2+ activity. Exposure of erythrocytes to supernatant of pathogens similarly induced eryptosis, an effect correlating with sphingomyelinase activity. The present observations disclose a novel pathophysiological mechanism leading to anemia and derangement of microcirculation during sepsis. Exposure to plasma from septic patients triggers phosphatidylserine exposure leading to adherence to the vascular wall and clearance from circulating blood.
Kempe
Daniela S
DS
Department of Physiology, University of Tübingen, Tübingen, Germany.
Akel
Ahmad
A
Lang
Philipp A
PA
Hermle
Tobias
T
Biswas
Raja
R
Muresanu
Juliana
J
Friedrich
Björn
B
Dreischer
Peter
P
Wolz
Christiane
C
Schumacher
Ulrike
U
Peschel
Andreas
A
Götz
Friedrich
F
Döring
Gerd
G
Wieder
Thomas
T
Gulbins
Erich
E
Lang
Florian
F
D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D001419:Bacteria; D001772:Blood Cell Count; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D002518:Ceramides / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D004912:Erythrocytes / Q000382:microbiology / Q000473:pathology*; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000473:pathology*
D017304:Annexin A5; D002518:Ceramides; D010718:Phosphatidylserines; D002118:Calcium