Down-regulation of tight junction mRNAs in human endothelial cells co-cultured with Plasmodium falciparum-infected erythrocytes.

To understand the mechanism of sequestration in the microvasculature of patients with falciparum malaria, we examined the patterns of expression of mRNAs for adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and tight junction molecules (occludin, vinculin, and ZO-1) in human umbilical vein endothelial cells (HUVECs) co-cultured with Plasmodium falciparum-parasitized red blood cells (PRBCs) in vitro. The PRBCs were collected from patients with uncomplicated, severe, or cerebral malaria (CM). Patterns of mRNA expression in HUVECs co-cultured with PRBCs were examined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Levels of mRNAs for all the three adhesion molecules increased with increased culture time within 3 h, regardless of the source of the PRBCs. In contrast, the patterns of mRNA expression for the tight junction molecules varied between the different co-cultures. When HUVECs were cultured with PRBCs from uncomplicated malaria patients, levels of mRNAs for tight junction molecules increased according to the culture time. HUVECs co-cultured with PRBCs from severe malaria patients showed no change in the mRNAs levels during 3 h of observation. When HUVECs were cultured with PRBCs from CM patients, levels of mRNAs for tight junction proteins decreased according to the culture time. Although the mechanisms underlying these phenomena are not clear, our results suggest that PRBCs can alter expression of tight junction proteins in endothelial cells at the site of sequestration and thereby influence disease severity.