Polyethylene glycol–coated red blood cells fail to bind glycophorin A–specific antibodies and are impervious to invasion by the Plasmodium falciparum malaria parasite
| Autor: | Jonathan K. Armstrong, Herbert J. Meiselman, Timothy C. Fisher, Douglas P. Blackall |
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| Rok vydání: | 2001 |
| Předmět: |
Erythrocytes
Hemagglutination Plasmodium falciparum Immunology Protozoan Proteins Antigens Protozoan Antigen-Antibody Complex CHO Cells Transfection Biochemistry Epitope Polyethylene Glycols Epitopes Antibody Specificity Cricetinae hemic and lymphatic diseases parasitic diseases PEG ratio Cell Adhesion medicine Animals Glycophorin Glycophorins Dose-Response Relationship Drug biology Antibodies Monoclonal hemic and immune systems Cell Biology Hematology biology.organism_classification Virology Molecular biology Red blood cell medicine.anatomical_structure Cerebral Malaria biology.protein Antibody Carrier Proteins Protein Binding |
| Zdroj: | Blood. 97:551-556 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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 byPlasmodium 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. |
| Databáze: | OpenAIRE |
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