Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx

Malaria Journal

Research

Jørgen Anders Lindholm Kurtzhals¹  Casper Hempel²  Trine Staalsø³  Christian William Wang⁴ 

[1] Department of Clinical Microbiology, Centre for Medical Parasitology, Copenhagen University Hospital, Copenhagen, Denmark;Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Clinical Microbiology, Centre for Medical Parasitology, Copenhagen University Hospital, Copenhagen, Denmark;Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Micro- and Nanotechnology, Technical University of Denmark, Kongens Lyngby, Denmark;Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark;

关键词: Plasmodium falciparum;    Endothelial glycocalyx;    Cytoadhesion;    Malaria;    Var;    Azido sugars;   

DOI  :  10.1186/s12936-017-1844-6

 received in 2017-03-06, accepted in 2017-04-27,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPlasmodium 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.MethodsGlycocalyx 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.ResultsThe 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.ConclusionThe 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.

【 授权许可】

CC BY   
© The Author(s) 2017