Effects of darbepoetin injections on erythrocyte membrane transport protein expressions in humans.

The present study investigated the effects of injected darbepoetin [novel erythropoietin stimulating protein (NESP)] on the density of three erythrocyte membrane transport proteins: the lactate-H+ cotransporter (monocarboxylate transporter 1), the chloride/bicarbonate exchanger 1 (anion exchanger 1), and the water channel aquaporin 1. Thirteen subjects were injected with NESP once a week for 4 wk. Blood samples were obtained before, during, and after the injection period, and the erythrocyte transport proteins were determined by Western blotting. The NESP injections induced a transient increase in hematocrit, red cell volume, and reticulocyte fraction. The density of aquaporin 1 protein was higher (maximal increase +59%) (P < 0.01) during the injection period compared with the preinjection value and lower (P < 0.01) after the injection period. The density of anion exchanger 1 protein was higher (maximal increase +15%) (P < 0.05) during the injection period compared with the preinjection value and tended (P = 0.06) to be lower after the injection period than before the injection period. The density of the erythrocyte monocarboxylate transporter 1 protein was higher (maximal increase +43%) (P < 0.05) during the injection period than in the preinjection period. Age separation experiments using self-creating Percoll gradients demonstrated a higher density of membrane transport proteins in young red blood cells. These data suggest that the NESP-induced increase in membrane transport proteins is caused by a higher fraction of newly formed erythrocytes (and reticulocytes), which have a higher density of membrane transport proteins. However, increased incorporation of membrane proteins during erythrocyte formation may also be involved. We suggest that NESP improves the quality of erythrocyte membrane transport through these mechanisms.