Synchronized cultures of P falciparum in abnormal red cells: the mechanism of the inhibition of growth in HbCC cells

Abstract

It has been previously demonstrated that HbCC cells fail to support growth of P falciparum in asynchronous Jensen-Trager cultures. To define the mechanism of inhibition we have studied synchronous cultures and found that while intraerythrocytic parasite development appeared normal, the liberation of merozoites and/or invasion was impaired. This effect was detected by a normal growth during the first growth cycle but dramatically reduced number of ring forms following the schizont stage. A specific test for the invasion of CC cells by P falciparum merozoites, nevertheless, was normal. The defect found in infected CC cells was not modified by changes in O2 tension (which altered the ligand saturation of Hb C) nor by the extracellular K+ concentration (excluding a K+ leak-dependent mechanism for the growth inhibition). The osmotic lysis of late-staged parasitized red cells revealed that 25% of infected AA cells were lysed when the extracellular medium was 95 mOsm. In contrast, infected CC cells required a decrease to 10 mOsm in the extracellular media to reach 25% lysis. We conclude that CC red cells are unsuitable hosts for the malarial parasite primarily because of their inability to lyse and release merozoites at the appropriate stage of intraerythrocytic development of P falciparum.