Blood, 15 January 2001, Vol. 97, No. 2, pp. 551-556
TRANSFUSION MEDICINE
Polyethylene glycol-coated red blood cells fail to bind
glycophorin A-specific antibodies and are impervious to invasion by
the Plasmodium falciparum malaria parasite
Douglas P. Blackall,
Jonathan K. Armstrong,
Herbert
J. Meiselman, and
Timothy C. Fisher
From the Department of Pathology, University of
Tennessee, Memphis, and the Department of Physiology and Biophysics,
University of Southern California School of Medicine, Los Angeles.
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.
