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39, No. 5, 2012
Issue release date: October 2012
Section title: Review Article · Übersichtsarbeit
Free Access
Transfus Med Hemother 2012;39:308–314
(DOI:10.1159/000342534)

Physiology and Pathophysiology of Eryptosis

Lang F. · Lang E. · Föller M.
Department of Physiology, University of Tübingen, Germany
email Corresponding Author

Abstract

Suicidal erythrocyte death (eryptosis) is characterized by cell shrinkage, cell membrane blebbing, and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Eryptotic cells adhere to the vascular wall and are rapidly cleared from circulating blood. Eryptosis is stimulated by an increase in cytosolic Ca2+ activity, ceramide, hyperosmotic shock, oxidative stress, energy depletion, hyperthermia, and a wide variety of xenobiotics and endogenous substances. Inhibitors of eryptosis include erythropoietin and nitric oxide. Enhanced eryptosis is observed in diabetes, renal insufficiency, hemolytic uremic syndrome, sepsis, mycoplasma infection, malaria, iron deficiency, sickle cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase-(G6PD) deficiency, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria, Wilson’s disease, myelodysplastic syndrome, and phosphate depletion. Eryptosis is further enhanced in gene-targeted mice with deficient annexin 7, cGMP-dependent protein kinase type I (cGKI), AMP-activated protein kinase (AMPK), anion exchanger 1 (AE1), adenomatous polyposis coli (APC), and Klotho, as well as in mouse models of sickle cell anemia and thalassemia. Decreased eryptosis is observed in mice with deficient phosphoinositide-dependent kinase 1 (PDK1), platelet activating factor (PAF) receptor, transient receptor potential channel 6 (TRPC6), janus kinase 3 (JAK3), and taurine transporter (TAUT). Eryptosis may be a useful mechanism to remove defective erythrocytes prior to hemolysis. Excessive eryptosis may, however, compromise microcirculation and lead to anemia.

© 2012 S. Karger AG, Basel


  

Keywords

  • Erythrocytes
  • Apoptosis
  • Anemia
  • Malaria
  • Iron deficiency
  • HUS
  • Sepsis
  • Renal insufficiency
  • Diabetes

  

Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut der Universitat Tubingen
Gmelinstr. 5, 72076 Tubingen, Germany
Tel. +49 7071 29-72194, Fax -5618
florian.lang@uni-tuebingen.de

  

Article Information

Received: May 8, 2012
Accepted: August 14, 2012
Published online: September 6, 2012
Number of Print Pages : 7

  

Publication Details

Transfusion Medicine and Hemotherapy

Vol. 39, No. 5, Year 2012 (Cover Date: October 2012)

Journal Editor: Sibrowski W. (Münster)
ISSN: 1660-3796 (Print), eISSN: 1660-3818 (Online)

For additional information: http://www.karger.com/TMH


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Suicidal erythrocyte death (eryptosis) is characterized by cell shrinkage, cell membrane blebbing, and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Eryptotic cells adhere to the vascular wall and are rapidly cleared from circulating blood. Eryptosis is stimulated by an increase in cytosolic Ca2+ activity, ceramide, hyperosmotic shock, oxidative stress, energy depletion, hyperthermia, and a wide variety of xenobiotics and endogenous substances. Inhibitors of eryptosis include erythropoietin and nitric oxide. Enhanced eryptosis is observed in diabetes, renal insufficiency, hemolytic uremic syndrome, sepsis, mycoplasma infection, malaria, iron deficiency, sickle cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase-(G6PD) deficiency, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria, Wilson’s disease, myelodysplastic syndrome, and phosphate depletion. Eryptosis is further enhanced in gene-targeted mice with deficient annexin 7, cGMP-dependent protein kinase type I (cGKI), AMP-activated protein kinase (AMPK), anion exchanger 1 (AE1), adenomatous polyposis coli (APC), and Klotho, as well as in mouse models of sickle cell anemia and thalassemia. Decreased eryptosis is observed in mice with deficient phosphoinositide-dependent kinase 1 (PDK1), platelet activating factor (PAF) receptor, transient receptor potential channel 6 (TRPC6), janus kinase 3 (JAK3), and taurine transporter (TAUT). Eryptosis may be a useful mechanism to remove defective erythrocytes prior to hemolysis. Excessive eryptosis may, however, compromise microcirculation and lead to anemia.

© 2012 S. Karger AG, Basel


  

Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut der Universitat Tubingen
Gmelinstr. 5, 72076 Tubingen, Germany
Tel. +49 7071 29-72194, Fax -5618
florian.lang@uni-tuebingen.de

  

Article Information

Received: May 8, 2012
Accepted: August 14, 2012
Published online: September 6, 2012
Number of Print Pages : 7

  

Publication Details

Transfusion Medicine and Hemotherapy

Vol. 39, No. 5, Year 2012 (Cover Date: October 2012)

Journal Editor: Sibrowski W. (Münster)
ISSN: 1660-3796 (Print), eISSN: 1660-3818 (Online)

For additional information: http://www.karger.com/TMH


Article / Publication Details

First-Page Preview
Abstract of Review Article · Übersichtsarbeit

Accepted: 8/14/2012
Published online: 9/6/2012
Issue release date: October 2012

Number of Print Pages: 0
Number of Figures: 0
Number of Tables: 0

ISSN: 1660-3796 (Print)
eISSN: 1660-3818 (Online)

For additional information: http://www.karger.com/TMH


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.