Erythrocytic mechanism of sickle cell resistance to malaria

The physiological basis for the resistance to falciparum malaria individuals with sickle cell trait has not been understood. Recent advances in erythrocytic Plasmodium falciparum culture have made possible a direct investigation of the development of the malaria parasite in cells with sickle cell homoglobin. In a high (18%) oxygen atmosphere, there is no apparent sickling of cells, and the growth and multiplication of P. falciparum is identical in normal (AA), hemoglobin S homozygous (SS), and hemoglobin S heterozygous (SA) erythrocytes. Cultures under low (1-5%) oxygen, however, showed clear inhibition of growth. The sickling of SS red cells killed and lysed most or all of the intracellular parasites. Parasites in SA red cells were killed primarily at the large ring stage, probably as a result of a disruption of the parasite metabolism. Incubation in cyanate prior to culture reversed the resistance of SA erythrocytes to plasmodium growth, but had no effect on SS red cell sickling or resistance. Thus, the mechanism of resistance in vivo may be due solely to intraerythrocytic conditions.