Effects of some biologically active compounds on phagosome-lysosome fusion in peritoneal macrophages of mice.
Effects of biologically active compounds bilirubin (BR), farmorubicin (FR), and chelerythrine (CR) on phagosome-lysome (P-L) fusion in mouse peritoneal macrophages were studied using fluorescent dye acridine orange as lysosomal labelling and yeast cells as target. It was found that all three compounds tested enhanced P-L fusion. To investigate mechanisms of these effects, changes in fluidity of rat liver lysosomal membranes under influence of BR, FR and CR were studied by measuring fluorescence intensity, lifetime, and polarization of DPH or TMA-DPH incorporated in isolated rat liver lysosomes. In order to characterize the cytoskeleton changes under the action of these biologically active compounds F-actin content in peritoneal macrophages of mice was determined. Our results demonstrate that BR action induces a decrease in DPH and TMA-DPH polarization, FR increases DPH and TMA-DPH polarization, and CR causes only an increase in TMA-DPH polarization in lysosomal membranes. All three compounds tested increase F-actin content in peritoneal macrophages. Thus, the effect of BR on P-L fusion is connected with increasing fluidity of lysosomal membranes and the cytoskeleton changes. The enhancement of P-L fusion under the action of FR and CR can most likely be explained by changes of the cytoskeleton state.
D000199:Actins / Q000032:analysis; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001663:Bilirubin / Q000494:pharmacology*; D002478:Cells, Cultured; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015251:Epirubicin / Q000494:pharmacology*; D005456:Fluorescent Dyes; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008561:Membrane Fusion / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D010617:Phenanthridines / Q000494:pharmacology*; D051381:Rats