Blood, 15 February 2002, Vol. 99, No. 4, pp. 1101-1101
Arginine supplementation improves the hydration of sickle
cells in a mouse model
The polymerization rate of sickle hemoglobin (HbS) is
exquisitely sensitive to its concentration. Since the amount of HbS in
a sickle cell is essentially fixed, the concentration is determined by
cell volume, which in turn depends on the cellular content of
monovalent cations. Sickle cells tend to become potassium depleted, leading to dehydration and increased polymerization and sickling. These
observations made apparent the need to understand the cation transport
properties of sickle cells, and it is now generally agreed that there
are 3 major contributors: KCl cotransport, sickling-induced permeability, and the calcium-activated K channel (also called the
Gardos channel in red cells).
Romero and colleagues (page 1103) have shown, in a mouse model of
sickle cell disease, that dietary arginine supplementation leads to
correction of low plasma arginine levels and partial normalization of
red cell hydration, with fewer dense, dehydrated cells. It seems likely
that this beneficial effect on cell hydration was a consequence of
decreased calcium-activated K-channel activity, since in the
arginine-supplemented group this transporter was shown to have a
lower activity after stimulation by ionophore-mediated calcium entry. Potassium efflux during deoxygenation in the presence of
calcium was also decreased and was most likely also due to inhibition
of the calcium-activated K channel. But an effect on sickling-induced permeability, which is thought to be responsible for calcium entry into the sickle cell, cannot be ruled out. There was
no change in the reticulocyte count after arginine
supplementation, which was disappointing in light of the
decreased K-channel activity and normalized cell density.
The potential significance of these results is increased by reports of
low plasma arginine in patients with sickle cell disease. Further
investigations are clearly needed to examine the mechanism by which
arginine influences red cell cation transport.
Robert S. Franco
University of Cincinnati
