[Effect of stimulation and inhibition of macrophage functions on hypercholesterolemia in rats].
In this study we investigated the effects of zymosan and prodigiozan, the macrophage stimulators, and GdCl3, a macrophage inhibitor, on blood lipoprotein composition, activities of liver cholesterly ester (CE) metabolising enzymes, incorporation of [14C]cholesterol (C) into bile acids and accumulation and synthesis of CE in peritoneal macrophages (PM) of rats fed with C-enriched diet for 7 days. The increase of number of phagocyte cells quantity in liver and blood colony-stimulating activity in rats pretreated with intravenous injection of zymosan and prodigiozan was accompanied by reduced C content in blood low density and very low density lipoproteins (LDL and VLDL), increase of liver lysosomal CE hydrolase activity (without change of acyl-CoA:C acyltransferase and cytoplasmatic CE hydrolase activities) and incorporation of labeled C into bile acids and decrease of CE formation and accumulation in PM in rats with hypercholesterolemia. In contrast, reduction of phagocyte population in liver caused by intravenous injection of GdCl3 was accompanied by enhancement of C and CE level in blood LDL and VLDL and decrease of lysosomal CE hydrolase activity and incorporation of C into bile acids in liver of C-feeding rats. The data obtained suggest that the stimulation of mononuclear phagocyte system may lead to a decrease of plasma C via activation of LDL and VLDL catabolism and induction of bile acid synthesis in liver.
Institute of Internal Medicine, Siberian Division of the Russian Academy of Medical Sciences, Vladimirovski st. 2a, Novosibirsk 630003, Russia.
P O
PO
Kuznetsov
A F
AF
Safina
Ia Sh
IaSh
Shvarts
D D
DD
Tsyrendorzhiev
A A
AA
Zubakhin
M I
MI
Dushkin
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002788:Cholesterol Esters / Q000097:blood; D003864:Depression, Chemical; D005682:Gadolinium / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000378:metabolism*; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D011354:Prodigiozan / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D013268:Stimulation, Chemical; D015054:Zymosan / Q000494:pharmacology
D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D015054:Zymosan; D011354:Prodigiozan; D002784:Cholesterol; D005682:Gadolinium; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase; C038958:gadolinium chloride