Platelet microparticles enhance Plasmodium falciparum‐parasitised red blood cell cytoadherence and activate human brain endothelial cells

Abstract

One of the mechanisms of cerebral malaria (CM) is the sequestration, within brain microvessels, of P. falciparum‐parasitised red blood cells (RBC), leucocytes and platelets. Besides, CM is characterised by an overproduction of pro‐inflammatory cytokines and endothelial activation with upregulation of adhesion molecules and microparticle (MP) release from vascular cells. MP are submicron membrane elements carrying on their surface proteins from their cell of origin. Platelets have been shown to modulate PRBC cytoadherence, thus we analysed the role of platelet MP in this binding. Confocal microscopy showed that MP adhered to and penetrated in human brain microvascular endothelial cells (HBEC). MP upregulated ICAM‐1 and VCAM‐1 expression on HBEC. Furthermore, MP adhered to parasitised, but also to normal RBC, as revealed by detection of CD41 on RBC. MP binding to RBC was not affected by temperature or phosphatidylserine blockade by annexin V, but was significantly reduced when PRBC were incubated with MP in the presence of blocking antibodies against platelet‐specific antigens. Lastly, MP, while interacting with the two other cell types, dramatically increased the binding of parasitised but also of normal RBC to HBEC and altered endothelial functions. MP thus appear to be an important element in RBC sequestration and in endothelial pathology, suggesting a novel mechanism in CM pathogenesis.