jasplakinolide and Chagas-Disease

The involvement of actin filaments from the host cell on the process of invasion of trypomastigote forms of Trypanosma cruzi was analyzed in seven different cell lines. Prior incubation of all cell lines with cytochalasin D, under conditions which interfere with actin filaments, markedly inhibited parasite internalization and increased parasite attachment. Attached parasites were readily ingested following washing of the drug-treated cells. Cytochalasin treatment interfered with the distribution of actin filaments of the host cell as evaluated by visualization of the filaments using confocal laser scanning microscopy of cells incubated in the presence of FITC-phalloidin. Concentration of actin filaments could be observed in most, but not all, parasites in the process of internalization. We also treated LLCMK 2 and macrophage cells with Jasplakinolide, a drug that stabilizes actin filaments, before interaction with the trypomastigote forms. This drug partially inhibits parasite invasion into the cells. Prior incubation of the host cells in the presence of colchicine, which interfere with microtubules, also inhibited parasite internalization into the cells.

Topics: Actin Cytoskeleton; Animals; Antineoplastic Agents; Chagas Disease; Chlorocebus aethiops; Colchicine; Cytochalasin D; Depsipeptides; Fluorescent Antibody Technique; Host-Parasite Interactions; Macrophages; Microscopy, Electron, Scanning; Nucleic Acid Synthesis Inhibitors; Peptides, Cyclic; Pseudopodia; Trypanosoma cruzi; Vero Cells