Publication Type:

Journal Article

Source:

Journal of Molecular Medicine, Volume 85, Number 3, p.273–281 (2007)

URL:

http://dx.doi.org/10.1007/s00109-006-0123-8

Abstract:

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.

Cite this Research Publication

D. S. Kempe, Akel, A., Lang, P. A., Hermle, T., Dr. Raja Biswas, Muresanu, J., Friedrich, B., Dreischer, P., Wolz, C., Schumacher, U., Peschel, A., Götz, F., Döring, G., Wieder, T., Gulbins, E., and Lang, F., “Suicidal erythrocyte death in sepsis”, Journal of Molecular Medicine, vol. 85, pp. 273–281, 2007.

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