Rheological analysis of the formation of rosettes by red blood cells parasitized by Plasmodium falciparum

Abstract

Red blood cells infected by mature malarial parasites of the species Plasmodium falciparum can adhere to non-parasitized red cells (rosetting) and also to endothelial cells (cytoadhesion). To investigate how the circulation might influence rosetting, we studied formation of rosettes in cell suspensions sheared in a cone-and-plate viscometer, and the ability of flowing non-parasitized cells to bind to parasitized cells already adherent to a surface. After rosettes of strain R29 had been disrupted with fucoidan, they reformed slowly under stationary conditions but more rapidly in suspensions sheared at low stress (about 0.1-0.2 Pa). Strain Malayan Camp gave a lower rosetting frequency which actually increased at low shear. Increasing shear stress was associated with reduction in rosette formation, although rosetting occurred at >1 Pa, suggesting that rosettes could form in the systemic circulation. Rosetting inhibited adhesion of flowing parasitized cells to immobilized platelets (which express the cytoadhesion receptor CD36), as evidenced by increased adhesion after disruption of rosettes. The de-rosetted adherent cells parasitized by R29 supported only a low level of rosetting when non-parasitized cells were flowed over them at a wall shear of 0.1 Pa, with little increase if the stress was decreased to 0.05 Pa. Rosettes formed in the circulation might obstruct microvessels and inhibit cytoadhesion if they reached venules. However, if cytoadhesion occurred before rosetting, then adherent cells should not efficiently form rosettes.