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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 372, Issue 3, pp 228–235 | Cite as

Inhibition of erythrocyte “apoptosis” by catecholamines

  • Philipp A. Lang
  • Daniela S. Kempe
  • Ahmad Akel
  • Barbara A. Klarl
  • Kerstin Eisele
  • Marlies Podolski
  • Tobias Hermle
  • Olivier M. Niemoeller
  • Philipp Attanasio
  • Stephan M. Huber
  • Thomas Wieder
  • Florian Lang
  • Christophe Duranton
Original Article

Abstract

Osmotic shock, oxidative stress and Cl removal activate a non-selective Ca2+-permeable cation conductance in human erythrocytes. The entry of Ca2+ leads to activation of a scramblase with subsequent exposure of phosphatidylserine at the cell surface. Phosphatidylserine mediates binding to phosphatidylserine receptors on macrophages which engulf and degrade phosphatidylserine exposing cells. Moreover, phosphatidylserine exposure may lead to adherence of erythrocytes to the vascular wall. In the present study, we explored whether activation of the non-selective cation conductance and subsequent phosphatidylserine exposure might be influenced by catecholamines. Phosphatidylserine exposure has been determined by FITC-annexin V binding while cell volume was estimated from forward scatter in FACS analysis. Removal of Cl enhanced annexin binding and decreased forward scatter, an effect significantly blunted by the β agonist isoproterenol (IC50 approx. 1 μM). Fluo-3 fluorescence measurements revealed an increase of cytosolic Ca2+ activity following Cl removal, an effect again significantly blunted by isoproterenol exposure (10 μM). Whole-cell patch-clamp experiments performed in Cl free bath solution indeed disclosed a time-dependent inactivation of a non-selective cation conductance following isoproterenol exposure (10 μM). Phenylephrine (IC50<10 μM), dobutamine (IC50 approx. 1 μM) and dopamine (IC50 approx. 3 μM) similarly inhibited the effect of Cl removal on annexin binding and forward scatter. In conclusion, several catecholamines inhibit the Cl removal-activated Ca2+ entry into erythrocytes, thus preventing increase of cytosolic Ca2+ activity, subsequent cell shrinkage and activation of erythrocyte scramblase. The catecholamines thus counteract erythrocyte phosphatidylserine exposure and subsequent clearance of erythrocytes from circulating blood.

Keywords

Annexin Calcium Catecholamines Cell volume Eryptosis Osmotic cell shrinkage 

Notes

Acknowledgements

The authors acknowledge the meticulous preparation of the manuscript by Tanja Loch. This study was supported by the Deutsche Forschungsgemeinschaft, No. La 315/4-3, La 315/13-1 and La 315/6-1, the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Center for Interdisciplinary Clinical Research) 01 KS 9602 and the Biomed program of the EU (BMH4-CT96-0602).

References

  1. Andree HA, Reutelingsperger CP, Hauptmann R, Hemker HC et al (1990) Binding of vascular anticoagulant alpha (VAC Alpha) to planar phospholipid bilayers. J Biol Chem 265:4923–4928PubMedGoogle Scholar
  2. Andrews DA, Yang L, Low PS (2002) Phorbol ester stimulates a protein kinase C-mediated agatoxin-TK-sensitive calcium permeability pathway in human red blood cells. Blood 100:3392–3399CrossRefPubMedGoogle Scholar
  3. Barry PH, Lynch JW (1991) Liquid junction potentials and small cell effects in patch-clamp analysis. J Membr Biol 121:101–117CrossRefPubMedGoogle Scholar
  4. Benjamin LJ, Manning JM (1986) Enhanced survival of sickle erythrocytes upon treatment with glyceraldehyde. Blood 67:544–546PubMedGoogle Scholar
  5. Berg CP, Engels IH, Rothbart A, Lauber K et al (2001) Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis. Cell Death Differ 8:1197–1206CrossRefPubMedGoogle Scholar
  6. Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21CrossRefPubMedGoogle Scholar
  7. Boas FE, Forman L, Beutler E (1998) Phosphatidylserine exposure and red cell viability in red cell aging and in hemolytic anemia. Proc Natl Acad Sci U S A 95:3077–3081CrossRefPubMedGoogle Scholar
  8. Bonomini M, Sirolli V, Gizzi F, Di Stante S et al (2002) Enhanced adherence of human uremic erythrocytes to vascular endothelium: role of phosphatidylserine exposure. Kidney Int 62:1358–1363PubMedCrossRefGoogle Scholar
  9. Bosman GJCGM, Willekens FLA, Werre JM (2005) Erythrocyte aging: a more than superficial resemblance to apoptosis? Cell Physiol Biochem 16:1–8CrossRefPubMedGoogle Scholar
  10. Brand VB, Sandu CD, Duranton C, Tanneur V et al (2003) Dependence of plasmodium falciparum in vitro growth on the cation permeability of the human host erythrocyte. Cell Physiol Biochem 13:347–356PubMedCrossRefGoogle Scholar
  11. Bratosin D, Estaquier J, Petit F, Arnoult D et al (2001) Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria. Cell Death Differ 8:1143–1156CrossRefPubMedGoogle Scholar
  12. Cabado AG, Vieytes MR, Botana LM (1994) Effect of ion composition on the changes in membrane potential induced with several stimuli in rat mast cells. J Cell Physiol 158:309–316CrossRefPubMedGoogle Scholar
  13. Chan HC, Goldstein J, Nelson DJ (1992) Alternate pathways for chloride conductance activation in normal and cystic fibrosis airway epithelial cells. Am J Physiol 262:C1273–C1283PubMedGoogle Scholar
  14. Closse C, Dachary-Prigent J, Boisseau MR (1999) Phosphatidylserine-related adhesion of human erythrocytes to vascular endothelium. Br J Haematol 107:300–302CrossRefPubMedGoogle Scholar
  15. Corash L, Spielberg S, Bartsocas C, Boxer L et al (1980) Reduced chronic hemolysis during high-dose Vitamin E administration in mediterranean-type glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 303:416–420PubMedCrossRefGoogle Scholar
  16. Damonte G, Guida L, Sdraffa A, Benatti U et al (1992) Mechanisms of perturbation of erythrocyte calcium homeostasis in favism. Cell Calcium 13:649–658CrossRefPubMedGoogle Scholar
  17. Daugas E, Cande C, Kroemer G (2001) Erythrocytes: death of a mummy. Cell Death Differ 8:1131–1133CrossRefPubMedGoogle Scholar
  18. Duranton C, Huber SM, Lang F (2002) Oxidation induces a Cl(-)-dependent cation conductance in human red blood cells. J Physiol 539:847–855CrossRefPubMedGoogle Scholar
  19. Duranton C, Huber S, Tanneur V, Lang K et al (2003) Electrophysiological properties of the plasmodium falciparum-induced cation conductance of human erythrocytes. Cell Physiol Biochem 13:189–198PubMedCrossRefGoogle Scholar
  20. Eda S, Sherman IW (2002) Cytoadherence of malaria-infected red blood cells involves exposure of phosphatidylserine. Cell Physiol Biochem 12:373–384CrossRefPubMedGoogle Scholar
  21. Fadok VA, Bratton DL, Rose DM, Pearson A et al (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85–90CrossRefPubMedGoogle Scholar
  22. Gallagher PG, Chang SH, Rettig MP, Neely JE et al (2003) Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis. Blood 101:4625–4627CrossRefPubMedGoogle Scholar
  23. Gamper N, Huber SM, Badawi K, Lang F (2000) Cell volume-sensitive sodium channels upregulated by glucocorticoids in U937 macrophages. Pflügers Archiv Eur J Physiol 441:281–286CrossRefGoogle Scholar
  24. Gulbins E, Jekle A, Ferlinz K, Grassme H et al (2000) Physiology of apoptosis. Am J Physiol Renal Physiol 279:F605–F615PubMedGoogle Scholar
  25. Harrison T, Samuel BU, Akompong T, Hamm H et al (2003) Erythrocyte G protein-coupled receptor signaling in malarial infection. Science 301:1734–1736CrossRefPubMedGoogle Scholar
  26. Hines PC, Zen Q, Burney SN, Shea DA et al (2003) Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-Dependent Sickle (SS) RBC adhesion. Blood 101:3281–3287CrossRefPubMedGoogle Scholar
  27. Huber SM, Gamper N, Lang F (2001) Chloride conductance and volume-regulatory nonselective cation conductance in human red blood cell ghosts. Pflügers Archiv Eur J Physiol 441:551–558CrossRefGoogle Scholar
  28. Kiefer CR, Snyder LM (2000) Oxidation and erythrocyte senescence. Curr Opin Hematol 7:113–116CrossRefPubMedGoogle Scholar
  29. Koch J, Korbmacher C (1999) Osmotic shrinkage activates Nonselective Cation (NSC) channels in various cell types. J Membr Biol 168:131–139CrossRefPubMedGoogle Scholar
  30. Lang KS, Roll B, Myssina S, Schittenhelm M et al (2002) Enhanced erythrocyte apoptosis in sickle cell anemia, Thalassemia and glucose-6-phosphate dehydrogenase deficiency. Cell Physiol Biochem 12:365–372CrossRefPubMedGoogle Scholar
  31. Lang KS, Duranton C, Poehlmann H, Myssina S et al (2003a) Cation channels trigger apoptotic death of erythrocytes. Cell Death Differ 10:249–256PubMedCrossRefGoogle Scholar
  32. Lang KS, Myssina S, Tanneur V, Wieder T et al (2003b) Inhibition of erythrocyte cation channels and apoptosis by ethylisopropylamiloride. Naunyn-Schmiedeberg's Arch Pharmacol 367:391–396CrossRefGoogle Scholar
  33. Lang PA, Kaiser S, Myssina S, Wieder T et al (2003c) Role of Ca2+-activated K+ channels in human erythrocyte apoptosis. Am J Physiol Cell Physiol 285:C1553–C1560PubMedGoogle Scholar
  34. Lang PA, Warskulat U, Heller-Stilb B, Huang DY et al (2003d) Blunted apoptosis of erythrocytes from taurine transporter deficient mice. Cell Physiol Biochem 13:337–346PubMedCrossRefGoogle Scholar
  35. Lang KS, Myssina S, Brand V, Sandu C et al (2004a) Involvement of ceramide in hyperosmotic shock-induced death of erythrocytes. Cell Death Differ 11:231–243CrossRefPubMedGoogle Scholar
  36. Lang KS, Myssina S, Lang PA, Tanneur V et al (2004b) Inhibition of erythrocyte phosphatidylserine exposure by Urea and Cl-. Am J Physiol Renal Physiol 286:F1046–F1053CrossRefPubMedGoogle Scholar
  37. Lang KS, Lang PA, Bauer C, Duranton C et al (2005a) Mechanisms of suicidal erythrocyte death. Cell Physiol Biochem 15:195–202CrossRefPubMedGoogle Scholar
  38. Lang PA, Kempe DS, Myssina S, Tanneur V et al (2005b) PGE(2) in the regulation of programmed erythrocyte death. Cell Death Differ 12:415–428CrossRefPubMedGoogle Scholar
  39. Maeno E, Ishizaki Y, Kanaseki T, Hazama A et al (2000) Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci U S A 97:9487–9492CrossRefPubMedGoogle Scholar
  40. Manodori AB, Barabino GA, Lubin BH, Kuypers FA (2000) Adherence of phosphatidylserine-exposing erythrocytes to endothelial matrix thrombospondin. Blood 95:1293–1300PubMedGoogle Scholar
  41. Michea L, Ferguson DR, Peters EM, Andrews PM et al (2000) Cell cycle delay and apoptosis are induced by high salt and urea in renal medullary cells. Am J Physiol Renal Physiol 278:F209–F218PubMedGoogle Scholar
  42. Myssina S, Lang PA, Kempe DS, Kaiser S et al (2004) Cl- channel blockers NPPB and niflumic acid blunt Ca(2+)-induced erythrocyte ‘apoptosis’. Cell Physiol Biochem 14:241–248CrossRefPubMedGoogle Scholar
  43. Nicotera P, Orrenius S (1998) The role of calcium in apoptosis. Cell Calcium 23:173–180CrossRefPubMedGoogle Scholar
  44. Oonishi T, Sakashita K, Uyesaka N (1997) Regulation of red blood cell filterability by Ca2+ influx and CAMP-mediated signaling pathways. Am J Physiol 273:C1828–C1834PubMedGoogle Scholar
  45. Pavoni V, Verri M, Ferraro L, Volta CA et al (1998) Plasma dopamine concentration and effects of low dopamine doses on urinary output after major vascular surgery. Kidney Int Suppl 66:S75–S80PubMedGoogle Scholar
  46. Rice L, Alfrey CP (2005) The negative regulation of red cell mass by neocytolysis: physiologic and pathophysiologic manifestations. Cell Physiol Biochem 15:245–250CrossRefPubMedGoogle Scholar
  47. Roelofsen B (1991) Molecular architecture and dynamics of the plasma membrane lipid bilayer: the red blood cell as a model. Infection 19(Suppl 4):S206–S209CrossRefPubMedGoogle Scholar
  48. Roger F, Martin PY, Rousselot M, Favre H et al (1999) Cell shrinkage triggers the activation of mitogen-activated protein kinases by hypertonicity in the rat kidney medullary thick ascending limb of the henle's loop. Requirement of P38 kinase for the regulatory volume increase response. J Biol Chem 274:34103–34110CrossRefPubMedGoogle Scholar
  49. Romero PJ, Romero EA (1999) Effect of cell ageing on Ca2+ influx into human red cells. Cell Calcium 26:131–137CrossRefPubMedGoogle Scholar
  50. Rosette C, Karin M (1996) Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors. Science 274:1194–1197CrossRefPubMedGoogle Scholar
  51. Ruymann FB, Popejoy LA, Brouillard RB (1978) Splenic sequestration and ineffective erythropoiesis in hemoglobin E-beta-Thalassemia disease. Pediatr Res 12:1020–1023PubMedCrossRefGoogle Scholar
  52. Sager G (1982) Receptor binding sites for beta-adrenergic ligands on human erythrocytes. Biochem Pharmacol 31:99–104CrossRefPubMedGoogle Scholar
  53. Setty BN, Kulkarni S, Stuart MJ (2002) Role of erythrocyte phosphatidylserine in sickle red cell-endothelial adhesion. Blood 99:1564–1571CrossRefPubMedGoogle Scholar
  54. Sprague RS, Ellsworth ML, Stephenson AH, Lonigro AJ (2001) Participation of CAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release. Am J Physiol Cell Physiol 281:C1158–C1164PubMedGoogle Scholar
  55. Volk T, Fromter E, Korbmacher C (1995) Hypertonicity activates nonselective cation channels in mouse cortical collecting duct cells. Proc Natl Acad Sci U S A 92:8478–8482PubMedCrossRefGoogle Scholar
  56. Wali RK, Jaffe S, Kumar D, Kalra VK (1988) Alterations in organization of phospholipids in erythrocytes as factor in adherence to endothelial cells in diabetes mellitus. Diabetes 37:104–111PubMedCrossRefGoogle Scholar
  57. Wehner F, Sauer H, Kinne RK (1995) Hypertonic stress increases the Na+ conductance of rat hepatocytes in primary culture. J Gen Physiol 105:507–535CrossRefPubMedGoogle Scholar
  58. Wehner F, Böhmer C, Heinzinger H, van den BF et al (2000) The hypertonicity-induced Na(+) conductance of rat hepatocytes: physiological significance and molecular correlate. Cell Physiol Biochem 10:335–340PubMedCrossRefGoogle Scholar
  59. Yang XY, Qu Q, Yang TY, Chan WC et al (1988) Treatment of the Thalassemia syndrome with splenectomy. Hemoglobin 12:601–608PubMedCrossRefGoogle Scholar
  60. Zhou Q, Zhao J, Wiedmer T, Sims PJ (2002) Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1. Blood 99:4030–4038CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Philipp A. Lang
    • 1
  • Daniela S. Kempe
    • 1
  • Ahmad Akel
    • 1
  • Barbara A. Klarl
    • 1
  • Kerstin Eisele
    • 1
  • Marlies Podolski
    • 1
  • Tobias Hermle
    • 1
  • Olivier M. Niemoeller
    • 1
  • Philipp Attanasio
    • 1
  • Stephan M. Huber
    • 1
  • Thomas Wieder
    • 1
  • Florian Lang
    • 1
    • 2
  • Christophe Duranton
    • 1
  1. 1.Department of PhysiologyUniversity of TübingenTübingenGermany
  2. 2.Physiologisches InstitutUniversität TübingenTübingenGermany

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