Polyethylene glycol-coated red blood cells fail to bind glycophorin A-specific antibodies and are impervious to invasion by the Plasmodium falciparum malaria parasite.
This study was designed to assess the binding of glycophorin A-specific antibodies to polyethylene glycol (PEG)-modified red blood cells (RBCs) and evaluate their resistance to invasion by Plasmodium falciparum malaria parasites. RBCs were conjugated with a range of concentrations (0.05 to 7.5 mM) of activated PEG derivatives of either 3.35 or 18.5 kd molecular mass. The binding of glycophorin A-specific antibodies was assessed by hemagglutination and flow cytometry. PEG-modified RBCs were assessed for their ability to form rosettes around Chinese hamster ovary (CHO) cells transiently expressing the glycophorin A binding domain of EBA-175, a P falciparum ligand crucial to RBC invasion. PEG-RBCs were also tested for their ability to be invaded by the malaria parasite. RBCs coated with 3.35 and 18.5 kd PEG demonstrated a dose-dependent inhibition of glycophorin A-specific antibody binding, CHO cell rosetting, and P falciparum invasion. These results indicate that glycophorin A epitopes responsible for antibody and parasite binding are concealed by PEG coating, rendering these cells resistant to P falciparum invasion. These studies confirm the effectiveness of PEG modification for masking RBC-surface glycoproteins. This may provide a means to prevent alloimmunization in the setting of RBC transfusion and suggests a novel method to enhance the effectiveness of exchange transfusion for the treatment of cerebral malaria.
Blackall
D P
DP
Department of Pathology, University of Tennessee, Memphis, USA. blackall@ucla.edu
Armstrong
J K
JK
Meiselman
H J
HJ
Fisher
T C
TC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000187:drug effects; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects* / Q000469:parasitology*; D006021:Glycophorins / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D006384:Hemagglutination / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D000939:Epitopes; D006021:Glycophorins; D015800:Protozoan Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium; D011092:Polyethylene Glycols