Polyethylene glycol–coated red blood cells fail to bind glycophorin A–specific antibodies and are impervious to invasion by the Plasmodium falciparum malaria parasite

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 551-556 ◽  
Author(s):  
Douglas P. Blackall ◽  
Jonathan K. Armstrong ◽  
Herbert J. Meiselman ◽  
Timothy C. Fisher
Keyword(s):  
Polyethylene Glycol ◽  
Red Blood Cells ◽  
Falciparum Malaria ◽  
Blood Cells ◽  
Malaria Parasite ◽  
Chinese Hamster ◽  
Plasmodium Falciparum Malaria ◽  
Glycophorin A ◽  
Specific Antibodies ◽  
Dependent Inhibition

Abstract 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.

scholarly journals The Wrb antigen, a receptor for Plasmodium falciparum malaria, is located on a helical region of the major membrane sialoglycoprotein of human red blood cells

1983 ◽  
Vol 209 (1) ◽  
pp. 273-276 ◽  
Author(s):  
K Ridgwell ◽  
M J Tanner ◽  
D J Anstee
Keyword(s):  
Plasmodium Falciparum ◽  
Monoclonal Antibodies ◽  
Red Blood Cells ◽  
Falciparum Malaria ◽  
Blood Cells ◽  
Plasmodium Falciparum Malaria ◽  
Human Erythrocytes ◽  
Glycophorin A ◽  
Human Red Blood Cells ◽  
Helical Region

1. Immunoprecipitation of periodate/NaB3H4-labelled human erythrocytes using anti-Wrightb (Wrb) monoclonal antibodies showed that these antibodies specifically react with the major erythrocyte sialoglycoprotein alpha (glycophorin A). 2. Similar experiments on erythrocytes from the only known individual lacking the Wrb antigen but with otherwise normal sialoglycoproteins did not result in the immunoprecipitation of any sialoglycoprotein. 3. We suggest that the Wrb antigen is located on an alpha-helical region between residues 55 and 70 of sialoglycoprotein alpha.

scholarly journals Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3637-3647 ◽  
Author(s):  
M Alessio ◽  
NJ Greco ◽  
L Primo ◽  
D Ghigo ◽  
A Bosia ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Red Blood Cells ◽  
Falciparum Malaria ◽  
Blood Cells ◽  
Plasmodium Falciparum Malaria ◽  
Adenosine Diphosphate ◽  
Surface Glycoprotein ◽  
Morphologic Change ◽  
Complement Components ◽  
Substrate Protein

Abstract The surface glycoprotein CD36 (GPIV) is known to mediate the adhesion of Plasmodium falciparum malaria-infected red blood cells and to be a receptor for extracellular matrix proteins such as collagen and thrombospondin. The murine monoclonal IgM antibody NL07, which is specific for CD36, has now been shown to also be a potent inhibitor of the adhesion of P falciparum malaria-infected red blood cells to C32 melanoma cells. Treatment of platelets with NL07 monoclonal antibody resulted in rapid degranulation, release of ATP and serotonin, increase in [Ca2+]i, and tyrosine phosphorylation of a substrate protein of 130 kD. In about one-half of the experiments, activation with NL07 resulted in the formation of small aggregates of 10 to 30 platelets, whereas in the other half of the experiments, large aggregates were seen similar to those induced by adenosine diphosphate (ADP) and these large aggregates could be converted to the small aggregates by ATP alpha S or by AP-2 or other antibodies against GPIIb and/or IIIa. Microaggregates of 2 to 5 platelets were seen with Glanzmann's platelets that constitutively lack GPIIb/IIIa. Aggregate formation was not seen with heat-treated serum, in the presence of anti C1q antibodies, or when using C5-, C8-, or C9-deficient human sera. Although activation of platelets with purified complement components results in a slow morphologic change without aggregation, involvement of CD36 results in rapid complement-mediated activation leading to formation of small aggregates that is largely independent of GPIIb/IIIa and that, under certain circumstances, proceeds to the formation of large ADP-dependent aggregates.

scholarly journals Febrile temperature but not proinflammatory cytokines promotes phosphatidylserine expression on Plasmodium falciparum malaria-infected red blood cells during parasite maturation

2010 ◽  
Vol 77A (6) ◽  
pp. 515-523 ◽  
Author(s):  
Kovit Pattanapanyasat ◽  
Panudda Sratongno ◽  
Pattamawan Chimma ◽  
Supapart Chitjamnongchai ◽  
Korakot Polsrila ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Falciparum Malaria ◽  
Proinflammatory Cytokines ◽  
Blood Cells ◽  
Plasmodium Falciparum Malaria

Hemolytic Anemia and Thromobocytopenia Associated with Ischemic Brain Lesions in Patients with Acute Uncomplicated Plasmodium Falciparum Malaria.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1572-1572
Author(s):  
Gary M. Brittenham ◽  
Christina L.V. Tosti ◽  
Xavier Golay ◽  
Marc Van Cauteren ◽  
Varinee Lekprasert ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Corpus Callosum ◽  
Red Blood Cells ◽  
Falciparum Malaria ◽  
Blood Cells ◽  
Microvascular Obstruction ◽  
Plasmodium Falciparum Malaria ◽  
Brain Lesions ◽  
Uncomplicated Falciparum Malaria ◽  
The Brain

Abstract To examine the association between hemolysis in Plasmodium falciparum malaria and brain lesions in the absence of severe or cerebral malaria, we prospectively examined patients at the Bangkok Hospital for Tropical Diseases. We conducted standard physical, neurological and laboratory studies on 10 consecutive adult, non-immune patients admitted with acute uncomplicated falciparum malaria. MR studies of the brain, including T2-weighted and diffusion-weighted sequences, were performed within 24 hours of admission and repeated after 4 weeks using a 3.0 Tesla scanner (Gyroscan Intera Master, Philips). Each patient was fully conscious (Glasgow coma score 14 to 15) and had no abnormality detected on standard neurological evaluation. Within 24 hours, initial MR examinations found a restricted diffusion, ischemic, symmetrical midline lesion in the splenium of the corpus callosum of 4 (40%) of the 10 male patients. On admission, the 4 patients with a splenial lesion had a higher median hematocrit (44 vs. 32%, P<0.04), a higher mean serum indirect bilirubin (2.8 vs. 0.7 mg/dL, P<0.03) and lower mean platelet count (48,500 vs. 129,000 × 1000/microL, P<0.01), as well as a greater fall in hematocrit over the first 3 hospital days (7 vs. 1%, P<0.003) than the remaining 6 patients. No significant differences were found between the 4 patients with and the 6 patients without the splenial lesions with respect to mean age, days of fever before admission, parasite count on admission, parasite count after 24 hours of hospitalization (near the time of the initial MRI examination), and parasite or fever clearance time. After effective antimalarial treatment with artemisinin combination therapy, repeat studies 4 weeks later found resolution of the hematological differences between the groups and no residua of the splenial lesions. We conclude that reversible white matter injury was initially present in at least some nonimmune patients with acute uncomplicated falciparum malaria and resolved after early treatment with potent antimalarial drugs. P. falciparum modifies the surface of infected erythrocytes so that the parasitized red blood cells sequester by adhering to endothelial cells lining the microvasculature of vital organs, especially within the brain. The blood supply to the splenium of the corpus callosum may make this area particularly vulnerable to sequestration of parasitized red blood cells and microvascular obstruction. In addition, platelet-mediated autoagglutination has been reported with falciparum malaria in Thailand. In our patients, increased sequestration and destruction of both red blood cells and platelets in platelet-mediated autoagglutinates may have contributed to the severity of the hemolysis and thrombocytopenia as well as to the microvascular obstruction underlying the lesions in the splenium of the corpus callousum. Episodes of uncomplicated falciparum malaria may be an unrecognized source of neurological disease and disability in affected populations, both in southeast Asia and globally.

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