Intralysosomal accumulation of gadolinium and lysosomal damage during selective depression of liver macrophages in vivo.
Kinetics of gadolinium accumulation was studied by inductively coupled plasma-emission spectroscopy after intravenous injection of this agent (7.5 mg/kg) to CBA mice. Gadolinium exhibits lysosomotropic properties (long-term selective accumulation in lysosomes in vivo). Gadolinium uptake by hepatic cells attained maximum 1 h after its intravenous injection and remained at this level during the next day. Accumulation of gadolinium in hepatocytic lysosomes disturbed their osmotic properties (as was seen from the increase in free acid phosphatase activity, which persisted for 19 days). Serum activities of beta-D-galactosidase and beta-D-glucuronidase also increased (24-72 h and day 19). Selective depression of liver macrophages (24-48 h) was accompanied by a decrease in serum chitotriosidase activity. We conclude that accumulation of gadolinium in lysosomes of liver macrophages leads to their damage and elimination of a certain population of macrophages (primarily large cells). Changes in activity of serum lysosomal enzymes also reflect repopulation of liver macrophages.
Korolenko
T A
TA
State Research Institute of Physiology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk.
Dergunova
M A
MA
Alekseenko
T V
TV
Zhanaeva
S Ya
SY
Filyushina
E E
EE
Filatova
T G
TG
D000818:Animals; D005682:Gadolinium / Q000378:metabolism / Q000494:pharmacology*; D005966:Glucuronidase / Q000097:blood / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA
D005682:Gadolinium; D005966:Glucuronidase