Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx
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- Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx
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BACKGROUND: Plasmodium falciparum-infected erythrocytes sequester in the microcirculation due to interaction between surface-expressed parasite proteins and endothelial receptors. Endothelial cells are covered in a carbohydrate-rich glycocalyx that shields against undesired leukocyte adhesion. It was investigated if the cellular glycocalyx affects the binding of P. falciparum-infected erythrocytes to CD36 in vitro.
METHODS: Glycocalyx growth was followed in vitro by using azido sugars and cationized ferritin detecting O-glycoproteins and negatively charged proteoglycans, respectively. P. falciparum (clone FCR3/IT) was selected on Chinese hamster ovary (CHO) cells transfected with human CD36. Cytoadhesion to CHO CD36 at 1-4 days after seeding was quantified by using a static binding assay.
RESULTS: The glycocalyx thickness of CHO cells increased during 4 days in culture as assessed by metabolic labelling of glycans with azido sugars and with electron microscopy studying the binding of cationized ferritin to cell surfaces. The functional importance of this process was addressed in binding assays by using CHO cells transfected with CD36. In parallel with the maturation of the glycocalyx, antibody-binding to CD36 was inhibited, despite stable expression of CD36. P. falciparum selected for CD36-binding recognized CD36 on CHO cells on the first day in culture, but the binding was lost after 2-4 days.
CONCLUSION: The endothelial glycocalyx affects parasite cytoadhesion in vitro, an effect that has previously been ignored. The previously reported loss of glycocalyx during experimental malaria may play an important role in the pathogenesis of malaria complications by allowing the close interaction between infected erythrocytes and endothelial receptors.
|Status||Udgivet - 10 maj 2017|
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