Mechanisms of suicidal erythrocyte death.
Erythrocyte injury such as osmotic shock, oxidative stress or energy depletion stimulates the formation of prostaglandin E2 through activation of cyclooxygenase which in turn activates a Ca2+ permeable cation channel. Increasing cytosolic Ca2+ concentrations activate Ca2+ sensitive K+ channels leading to hyperpolarization, subsequent loss of KCl and (further) cell shrinkage. Ca2+ further stimulates a scramblase shifting phosphatidylserine from the inner to the outer cell membrane. The scramblase is sensitized for the effects of Ca2+ by ceramide which is formed by a sphingomyelinase following several stressors including osmotic shock. The sphingomyelinase is activated by platelet activating factor PAF which is released by activation of phospholipase A2. Phosphatidylserine at the erythrocyte surface is recognised by macrophages which engulf and degrade the affected cells. Moreover, phosphatidylserine exposing erythrocytes may adhere to the vascular wall and thus interfere with microcirculation. Erythrocyte shrinkage and phosphatidylserine exposure ('eryptosis') mimic features of apoptosis in nucleated cells which however, involves several mechanisms lacking in erythrocytes. In kidney medulla, exposure time is usually too short to induce eryptosis despite high osmolarity. Beyond that high Cl- concentrations inhibit the cation channel and high urea concentrations the sphingomyelinase. Eryptosis is inhibited by erythropoietin which thus extends the life span of circulating erythrocytes. Several conditions trigger premature eryptosis thus favouring the development of anemia. On the other hand, eryptosis may be a mechanism of defective erythrocytes to escape hemolysis. Beyond their significance for erythrocyte survival and death the mechanisms involved in 'eryptosis' may similarly contribute to apoptosis of nucleated cells.
Lang
Karl S
KS
Department of Physiology, University of Tübingen, Germany.
Lang
Philipp A
PA
Bauer
Christian
C
Duranton
Christophe
C
Wieder
Thomas
T
Huber
Stephan M
SM
Lang
Florian
F
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D048429:Cell Size; D004912:Erythrocytes / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D007679:Kidney Medulla / Q000502:physiology; D051379:Mice; D010972:Platelet Activating Factor / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
D007473:Ion Channels; D010972:Platelet Activating Factor; D011453:Prostaglandins; D004921:Erythropoietin; D013108:Sphingomyelin Phosphodiesterase