MODULATED RED-BLOOD-CELL SURVIVAL BY MEMBRANE-PROTEIN CLUSTERING

Human and murine blood cells treated with ZnCl2 and bis(sulfosuccinimi dyl)suberate (BS3) (a cross linking agent) undergo band 3 clustering a nd binding of hemoglobin to red blood cell membrane proteins. These cl usters induce autologous IgG binding and complement fixation, thus fav ouring the phagocytosis of ZnCl2/BS3 treated cells by macrophages. The extension of red blood cell opsonization can be easily modulated by c hanging the ZnCl2 concentration in the 0.1-1.0 mM range thus providing an effective way to affect blood cell recognition by macrophages. In fact, murine erythrocytes treated with increasing ZnCl2 concentrations have proportionally reduced survivals when reinjected into the animal . Furthermore, the organ sequestration of ZnCl2/BS3 treated cells stro ngly resembles the typical distribution of the senescent cells. Since the ZnCl2/BS3 treatment can also be performed on red blood cells loade d with drugs or other substances, this procedure is an effective drug- targeting system to be used for the delivery of molecules to peritonea l, liver and spleen macrophages.