Chemical camouflage of antigenic determinants: Stealth erythrocytes

摘要: In a number of clinical circumstances it would be desirable to artificially conceal cellular antigenic determinants permit survival heterologous donor cells. A case in point is the problem encountered transfusions patients with rare blood types or chronically transfused who become allosensitized minor group determinants. We have tested possibility that chemical modification red cell (RBC) membrane might serve occlude determinants, thereby minimizing transfusion reactions. To this end, we covalently bound methoxy(polyethylene glycol) (mPEG) surface mammalian RBC via cyanuric chloride coupling. Human treated technique lose ABO reactivity as assessed by solution–phase antisera agglutination. accord this, also find profound decrease anti-blood antibody binding. Furthermore, whereas human monocytes avidly phagocytose untreated sheep RBC, mPEG-derivatized are ineffectively phagocytosed. Surprisingly, and mouse appear unaffected covalent membrane. Thus, mPEG-treated morphologically normal, normal osmotic fragility, murine vivo survival, even following repeated infusions. Finally, preliminary experiments, mPEG-modified intraperitoneally into mice show significantly improved (up 360-fold) when compared RBC. speculate similar camouflage intact cells may significant applications both (e.g., allosensitization autoimmune hemolytic disease) transplantation endothelial pancreatic β cells) medicine.