[The effect of biologically active compounds on lysosome fusion with phagosomes and the F-actin content in mouse peritoneal macrophages and on the status of the lysosomal membranes in mouse hepatocytes].

Effects of biologically active compounds bilirubin (BR, 0.1 and 0.2 mM), chelerythrine (CR, 0.1 and 0.5 mM) and farmorubicin (FR, 0.6 and 6.0 mM) on the phagosome-lysosome fusion (P-LF) were studied using fluorescent dye acridine orange for lysosomal labelling and yeast cells as a target. To investigate mechanisms of these effects, changes in fluidity of lysosomal membranes from murine liver were studied by measuring of fluorescence intensity, lifetime and polarization of the fluorescent membrane probes: DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH [1-(4-triphenylamino)-6-phenyl-1,3,5-hexatriene] incorporated in isolated murine liver lysosomes. In order to characterize the induced cytoskeleton changes, the F-actin content in murine peritoneal macrophages was determined. It was found that all three compounds tested enhanced P-LF. Our results demonstrate that BR induces a decrease in DPH and TMA-DPH fluorescence polarization, FR increases DPH and TMA-DPH fluorescence polarization, and CR causes an increase in TMA-DPH fluorescence polarization in lysosomal membranes. All the three compounds increase F-actin content in peritoneal macrophages. Thus, the action of BR extended on P-LF is associated with increasing lysosomal membranes fluidity and cytoskeleton changes. The enhancement of P-LF under the action of FR and CR can be most likely explained by changes of cytoskeleton.