Dijkstra J, van Galen M, Scherphof G.Effects of
dihydro-cytochalasin B, colchicine, monensin and trifluoperazine
on uptake and processing of liposomes by Kupffer cells in
culture.
Biochim Biophys Acta. 1985 Apr 22;845(1):34-42
We investigated the effects of (dihydro)cytochalasin B,
colchicine, monensin and trifluoperazine on uptake and
processing of large unilamellar liposomes by rat Kupffer cells
in maintenance culture. The phospholipid vesicles were labeled
in the lipid moiety with phosphatidyl[14C]choline and contained
[3H]inulin or [125I]iodoalbumin as nondegradable and degradable
markers of the aqueous vesicle content, respectively.
Cytochalasin B and dihydrocytochalasin B, inhibitors of
microfilament function, reduced inert inulin label uptake by 75%
maximally, but residual uptake was not followed by release of
lipid degradation products from the cells. By contrast,
colchicine, an inhibitor of microtubule assembly, reduced uptake
of liposomal inulin by maximally 55% but could not inhibit
release of lipid degradation products from the cells. It is
concluded that the cytochalasins partly inhibit uptake but fully
prevent the arrival of internalized liposomes in the lysosomal
compartment, while the action of colchicine is to slow down the
overall process of uptake and subsequent transportation to the
lysosomes. Monensin reduced inulin uptake to an extent similar
to that found with colchicine, but reversibly blocked
degradation of liposomal lipid and encapsulated protein. The
kinetics of degradation of liposomal constituents suggests that
residual uptake in the presence of monensin represents
accumulation in an intracellular compartment. Trifluoperazine
did not affect binding, internalization or degradation of
encapsulated protein at low concentration (6 microM), but
completely inhibited release of liposomal lipid degradation
products under these conditions. At intermediate concentration
(14 microM), the drug also reduced the internalization, while a
high concentration (22 microM) was required to inhibit protein
degradation as well. We conclude that trifluoperazine has
multiple sites of action in the uptake and processing of
liposomal constituents by Kupffer cells.
PMID: 3978127
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