cytochalasin-b and Malaria

Two structurally distinct ribosomal RNAs (rRNAs) occur in different developmental stages of malaria parasites. One point at which the transition from one type to the other is found shortly after sporozoites invade hepatocytes, the first stage of parasite development in the mammalian host. The invasion in itself appears necessary but insufficient to trigger the rRNA transition. The progression of events involved in the synthesis of a new type ribosome is tied to the fate of the invading parasite. Interestingly, the switch also occurs in irradiated sporozoites. The new rRNAs produced are processed to the mature size, indicating that rRNA transcription and processing remain normal in the attenuated parasites. These results have implications for monitoring antimalaria vaccine candidates and drug efficacy.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Protozoan; Base Sequence; Blotting, Northern; Cells, Cultured; Cytochalasin B; Gene Expression Regulation; Humans; In Vitro Techniques; Liver; Malaria; Molecular Sequence Data; Oligonucleotide Probes; Plasmodium; RNA Processing, Post-Transcriptional; RNA, Ribosomal; Transcription, Genetic

A monoclonal antibody directed against the circumsporozoite protein on the surface of Plasmodium berghei sporozoites inhibited sporozoite motility in vitro. These immobilized sporozoites could adhere to but not invade target cultured cells. Other sporozoite-immobilizing agents also inhibited sporozoite invasion into cultured cells and did not prevent sporozoite adherence. These results indicate that sporozoite invasiveness is associated with sporozoite motility. Thus, the immobilizing effect of this antibody could explain its functional activity against sporozoite invasion in vivo.

Topics: Adhesiveness; Animals; Antibodies, Monoclonal; Antibody Specificity; Antigen-Antibody Reactions; Antigens, Protozoan; Cell Line; Cells, Cultured; Cytochalasin B; Gamma Rays; Hot Temperature; Humans; Immunoenzyme Techniques; Immunoglobulin Fab Fragments; Malaria; Mice; Mice, Inbred A; Movement; Plasmodium berghei

Topics: Animals; Biological Transport; Cytochalasin B; Deoxyglucose; Erythrocytes; Glucose; Malaria; Mice; Phloretin; Plasmodium berghei

Invasion of erythrocytes by malarial merozoites requires the formation of a junction between the merozoite and the erythrocyte. Migration of the junction parallel to the long axis of the merozoite occurs during the entry of the merozoite into an invagination of the erythrocyte. Freeze-fracture shows a narrow circumferential band of rhomboidally arrayed particles on the P face of the erythrocyte membrane at the neck of the erythrocyte invagination and matching rhomboidally arrayed pits on the E face. The band corresponds to the junction between the erythrocyte and merozoite membranes observed in thin sections and may represent the anchorage sites of the contractile proteins within the erythrocyte. Intramembrane particles (IMP) on the P face of the erythrocyte membrane disappear beyond this junction. When the erythrocytes and cytochalasin B-treated merozoites are incubated together, the merozoite attaches to the erythrocyte membrane and a junction is formed between the two, but the invasion process does not advance further and no movement of the junction occurs. Although there is no entry of the parasite, the erythrocyte membrane still invaginates. Freeze-fracture shows that the P face of the invaginated erythrocyte membrane is almost devoid of the IMP that are found elsewhere on the membrane, suggesting that the attachment process in and of itself is sufficient to create a relatively IMP-free bilayer.

Topics: Animals; Cell Aggregation; Cytochalasin B; Erythrocyte Membrane; Erythrocytes; Freeze Fracturing; Malaria; Plasmodium