Prostaglandin E2 activates channel-mediated calcium entry in human erythrocytes: an indication for a blood clot formation supporting process

Lars Kaestner; Wiebke Tabellion; Peter Lipp; Ingolf Bernhardt

doi:10.1160/TH04-06-0338

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(06): 1269-1272
DOI: 10.1160/TH04-06-0338

Rapid and Short Communication

Schattauer GmbH

Prostaglandin E₂ activates channel-mediated calcium entry in human erythrocytes: an indication for a blood clot formation supporting process

Authors

Lars Kaestner

¹Institute for Molecular Cell Biology, Faculty of Medicine, Saarland University, Homburg/Saar, Germany
Wiebke Tabellion

¹Institute for Molecular Cell Biology, Faculty of Medicine, Saarland University, Homburg/Saar, Germany

²Laboratory of Biophysics, Faculty of Natural and Technical Sciences III, Saarland University, Saarbrücken, Germany
Peter Lipp

¹Institute for Molecular Cell Biology, Faculty of Medicine, Saarland University, Homburg/Saar, Germany
Ingolf Bernhardt

²Laboratory of Biophysics, Faculty of Natural and Technical Sciences III, Saarland University, Saarbrücken, Germany

Abstract

Summary

Prostaglandin E₂ (PGE₂) is released from platelets when they are activated. Using fluorescence imaging and the patch-clamp technique, we provide evidence that PGE₂ at physiological concentrations (10⁻¹⁰ M) activates calcium rises mediated by calcium influx through a non-selective cation-channel in human red blood cells. The extent of calcium increase varied between cells with a total of 45% of the cells responding. It is well known that calcium increases elicited the calcium-activated potassium channel (Gardos channel) in the red cell membrane. Previously, it was shown that the Gardos channel activation results in potassium efflux and shrinkage of the cells. Therefore, we conclude that the PGE₂ responses of red blood cells described here reveal a direct and active participation of erythrocytes in blood clot formation.

Keywords

Prostaglandin E₂ - erythrocytes - coagulation - fluorescence imaging - patch clamp

Full Text

References

References
1 Smith JB, Ingerman C, Kocsis JJ. et al. Formation of prostaglandins during the aggregation of human blood platelets. J Clin Invest 1973; 52: 965-9.
2 Oonishi T, Sakashita K, Ishioka N. et al. Production of Prostaglandins E1 and E2 by adult human red blood cells. Prostaglandins Other Lipid Mediat 1998; 56: 89-101.
3 Li Q, Jungmann V, Kiyatkin A. et al. Prostaglandin E2 stimulates a Ca2+-dependent K+ channel in human erythrocytes and alters cell volume and filterability. J Biol Chem 1996; 271: 18651-6.
4 Kaestner L, Bernhardt I. Ion channels in the human red blood cell membrane: their further investigation and physiological relevance. J Bioelectrochem 2002; 55: 71-4.
5 Christophersen P, Bennekou P. Evidence for a voltage-gated, non-selective cation channel in the human red cell membrane. Biochim Biophys Acta 1991; 1065: 103-6.
6 Kaestner L, Bollensdorff C, Bernhardt I. Nonselective voltage-activated cation channel in the human red blood cell membrane. Biochim Biophys Acta 1999; 1417: 9-15.
7 Kaestner L, Christophersen P, Bernhardt I. et al. The non-selective voltage-activated cation channel in the human red blood cell membrane: reconciliation between two conflicting reports and further characterisation. J Bioelectrochem 2000; 52: 117-25.
8 Soldati L, Lombardi C, Adamo D. et al. Arachidonic acid increases intracellular calcium in erythrocytes. Biochem Biophys Res Commun 2002; 293: 974-8.
9 Kucherenko YV, Weiss E, Bernhardt I. Effect of the ionic strength and prostaglandin E2 on the free Ca2+ concentration and the Ca2+ influx in human red blood cells. J Bioelectrochem 2004; 62: 127-33.
10 Blackwood AM, Sagnella GA, Markandu ND. et al. Problems associated with using Fura-2 to measure free intracellular calcium concentrations in human red blood cells. J Hum Hypertens 1997; 11: 601-4.
11 Yang L, Andrews DA, Low PS. Lysophosphatidic acid opens a Ca(++) channel in human erythrocytes. Blood 2000; 95: 2420-5.
12 Tiffert T, Bookchin RM, Lew VL. Calcium Homeostasis in Normal and Abnormal Human Red Cells. In: Red Cell Membrane Transport in Health and Disease. Springer Verlag; 2003: 373-405.
13 Bennekou P, Christophersen P. Ion Channels. In: Red Cell Membrane Transport in Health and Disease. Springer Verlag; 2003: 139-52.
14 Kaestner L. Passive elektrogene Transportprozesse durch die Membran von Humanerythrozyten und Erythrozyten von gesunden und Malaria-infizierten Hühnern. Berlin: Logos Verlag; 2001
15 Sarkadi B, Gardos G. Drug actions on Potassium fluxes in red cells. In: The red cell membrane. A model for solute transport. Humana press; 1989: 369-96.
16 Haest CWM. Distribution and Movement of Membrane Lipids. In: Red Cell Membrane Transport in Health and Disease. Springer Verlag; 2003: 1-26.
17 Woon LA, Holland JW, Kable EP. et al. Ca2+ sensitivity of phospholipid scrambling in human red cell ghosts. Cell Calcium 1999; 25: 313-20.
18 Lang KS, Duranton C, Poehlmann H. et al. Cation channels trigger apoptotic death of erythrocytes. Cell Death Differ 2003; 10: 249-56.
19 Hellem AJ. The adhesiveness of human blood platelets in vitro. Scand J Clin Lab Invest 1960; 12 (Suppl): 1-117.
20 Hellem AJ, Borchgrevink CF, Ames SB. The role of red cells in haemostasis: the relation between haematocrit, bleeding time and platelet adhesiveness. Br J Haematol 1961; 07: 42-50.
21 Saniabadi AR, Lowe GD, Barbenel JC. et al. Further studies on the role of red blood cells in spontaneous platelet aggregation. Thromb Res 1985; 38: 225-32.
22 Andrews DA, Yang L, Low PS. Phorbol ester stimulates a protein kinase C-mediated agatoxin-TK-sensitive calcium permeability pathway in human red blood cells. Blood 2002; 100: 3392-9.