Malaria and bacterial sepsis: similar mechanisms of endothelial apoptosis and its prevention in vitro.

Objective And Design: Apoptotic endothelial damage contributes to multiorgan failure in Plasmodium falciparum malaria and in sepsis. In malaria, endothelial apoptosis is amplified by neutrophils and their secretory products, and reduced by inhibitors of neutrophil-derived substances in vitro. We compared the mechanisms of endothelial apoptosis in malaria and in sepsis, using the human umbilical vein endothelial cell as a model.

Generation of cross-protective antibodies against Plasmodium falciparum sequestration by immunization with an erythrocyte membrane protein 1-duffy binding-like 1 alpha domain.

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important virulence factor on the surface of infected erythrocytes. Naturally acquired antibodies to PfEMP1 expressed by parasites causing severe malaria are suggested to be protective and of major interest for the development of a vaccine against severe disease. In this study, the PfEMP1 expressed by a parasite clone displaying a multiadhesive phenotype associated with severe malaria was well recognized by sera of malaria semi-immune children.

Release of sequestered malaria parasites upon injection of a glycosaminoglycan.

Severe human malaria is attributable to an excessive sequestration of Plasmodium falciparum-infected and uninfected erythrocytes in vital organs. Strains of P. falciparum that form rosettes and employ heparan sulfate as a host receptor are associated with development of severe forms of malaria.

Whole-body imaging of sequestration of Plasmodium falciparum in the rat.

The occlusion of vessels by packed Plasmodium falciparum-infected (iRBC) and uninfected erythrocytes is a characteristic postmortem finding in the microvasculature of patients with severe malaria. Here we have employed immunocompetent Sprague-Dawley rats to establish sequestration in vivo. Human iRBC cultivated in vitro and purified in a single step over a magnet were labeled with 99mtechnetium, injected into the tail vein of the rat, and monitored dynamically for adhesion in the microvasculature using whole-body imaging or imaging of the lungs subsequent to surgical removal.

Immunization with PfEMP1-DBL1alpha generates antibodies that disrupt rosettes and protect against the sequestration of Plasmodium falciparum-infected erythrocytes.

A family of parasite antigens known as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is believed to play an important role in the binding of infected erythrocytes to host receptors in the micro-vasculature. Available data advocates the existence of a subset of very adhesive (rosetting, auto-agglutinating) and antigenic PfEMP1s implicated as virulence factors. Serum antibodies that disrupt rosettes are rarely found in children with severe malaria but are frequent in those with mild disease suggesting that they may be protective.

Heparan sulphate identified on human erythrocytes: a Plasmodium falciparum receptor.

HS (heparan sulphate) has hitherto not been found on human red blood cells (RBCs, erythrocytes). However, malarial-parasite (Plasmodium falciparum)-infected RBCs adhere to uninfected RBCs via HS-like receptors. In the present paper we demonstrate that human RBCs carry epitopes for an anti-HS antibody.

Heparan sulfate on endothelial cells mediates the binding of Plasmodium falciparum-infected erythrocytes via the DBL1alpha domain of PfEMP1.

Plasmodium falciparum may cause severe forms of malaria when excessive sequestration of infected and uninfected erythrocytes occurs in vital organs. The capacity of wild-type isolates of P falciparum-infected erythrocytes (parasitized red blood cells [pRBCs]) to bind glycosaminoglycans (GAGs) such as heparin has been identified as a marker for severe disease. Here we report that pRBCs of the parasite FCR3S1.