Malaria and the red cell membrane

Malarial parasites are primarily parasites of red cells and during infection ingest most of the haemoglobin within these cells, leaving the membrane as the only vestige of the original host cell. The red cell membrane thus plays a key role at all stages of infection with malarial parasites, and is modified in many ways during parasitisation, so that at least functionally it has little resemblance to the membrane from which it was originally derived. The highly specific and ordered process of parasite invasion of red cells is regulated at least in part by the uninfected red cell membrane. The red cell sialoglycoproteins or glycophorins of this membrane have been shown to play an important role in invasion by Plasmodium falciparum, the species of most importance to man because of it's high morbidity and mortality. Structurally, dynamic changes occur within the membrane during parasitisation, and a number of parasite proteins have been found to be associated within it, but changes on the surface of the infected cell have been more difficult to demonstrate. The membrane of the infected cell in important in the many metabolic processes of the parasite, as well as the critical cell-cell interactions that occur when cells containing mature parasites bind to endothelial cells (cytoadherence), bind to uninfected cells (rosetting), or interact with macrophages and other leucocytes. The recognition molecules on the red cell membrane involved in invasion, cytoadherence and rosetting appear to be quite distinct. Structural and functional changes have also been shown to occur in the membranes of uninfected red cells, both in infected patients, and in the presence of parasites in vitro. Interactions of the parasite P. falciparum with the red cell membrane hold the key to our understanding of the pathogenesis of severe falciparum infection in man.