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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4853-4860.
Prepublished online as a Blood First Edition Paper on February 22, 2005; DOI 10.1182/blood-2004-12-4948.


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Submitted December 30, 2004
Accepted February 17, 2005

The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum

Teresa Tiffert*, Virgilio L Lew, Hagai Ginsburg, Miriam Krugliak, Laure Croisille, and Narla Mohandas

Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom
Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
New York Blood Center, New York, NY, USA

* Corresponding author; email: jtt1000{at}cam.ac.uk.

In most inherited red blood cell (RBC) disorders with high gene frequencies in malaria endemic regions, the distribution of red cell hydration states is much wider than normal. The relation between hydration state of circulating RBCs and protection against severe falciparum malaria remains unexplored. The present investigation was prompted by a casual observation suggesting that falciparum merozoites were unable to invade isotonically dehydrated normal RBCs. We designed an experimental model to induce uniform and stable isotonic volume changes in RBC populations from healthy donors by increasing or decreasing their KCl contents through a reversible K+ permeabilization pulse. Swollen and mildly dehydrated RBCs were able to sustain P. falciparum cultures with similar efficiency to untreated RBCs. However, parasite invasion and growth were progressively reduced in dehydrated RBCs. In a parallel study, P. falciparum invasion was investigated in density-fractionated RBCs from normal subjects and from individuals with inherited RBC abnormalities affecting primarily hemoglobin or the RBC membrane (thalassemias, hereditary ovalocytosis, xerocytosis, Hb CC and Hb SC). Invasion was invariably reduced in the dense cell fractions in all conditions. These results suggest that the presence of dense RBCs is a protective factor, additional to any other protection mechanism prevailing in each of the different pathologies.


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