Modulated red blood cell survival by membrane protein clustering.
Human and murine blood cells treated with ZnCl2 and bis(sulfosuccinimidyl)suberate (BS3) (a cross linking agent) undergo band 3 clustering and binding of hemoglobin to red blood cell membrane proteins. These clusters induce autologous IgG binding and complement fixation, thus favouring the phagocytosis of ZnCl2/BS3 treated cells by macrophages. The extension of red blood cell opsonization can be easily modulated by changing 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 strongly resembles the typical distribution of the senescent cells. Since the ZnCl2/BS3 treatment can also be performed on red blood cells loaded with drugs or other substances, this procedure is an effective drug-targeting system to be used for the delivery of molecules to peritoneal, liver and spleen macrophages.
Chiarantini
L
L
Institute of Biochemistry Giorgio Fornaini, University of Urbino, (PS) Italy.
Rossi
L
L
Fraternale
A
A
Magnani
M
M
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004905:Erythrocyte Aging / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D051379:Mice; D013388:Succinimides / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology
D001457:Anion Exchange Protein 1, Erythrocyte; D001798:Blood Proteins; D002712:Chlorides; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D007074:Immunoglobulin G; D013388:Succinimides; D017967:Zinc Compounds; C016837:zinc chloride; C035760:bis(sulfosuccinimidyl)suberate