The influence of endotoxin in vitro on hepatic macrophage lysosomal enzyme release in different rat models of hepatic injury.
Since bacterial endotoxin is known to be involved in the pathogenesis of hepatic injury, the influence of endotoxin on lysosomal enzyme production by hepatic macrophages has been investigated. Macrophages have been isolated from the livers of normal rats, from the livers of rats given stilboestrol subcutaneously 4 days previously and from the livers of rats given Corynebacterium parvum intravenously 6 days previously. Following isolation and overnight culture, the macrophages have been maintained in in vitro culture for a further 24 h and the production of N-acetyl-beta-glucosaminidase (NAG) has been measured. Histological assessment has shown that in stilboestrol model an approximate doubling of sinusoidal cell numbers occurs and in the C. parvum model a heavy mononuclear cell infiltrate is present, together with granuloma formation. These changes are reflected in the numbers of macrophages isolated from the respective models. Levels of NAG production by resident macrophages from normal livers are low (0.25 +/- 0.05 nmol substrate hydrolysed/microgram cell protein/h) and unchanged following endotoxin exposure (0.25 +/- 0.05 units). Macrophages isolated from the stilboestrol model show levels of NAG production similar to normal (0.34 +/- 0.06 units), but this increases significantly following exposure to endotoxin (0.42 +/- 0.07 units). Macrophages from the C. parvum model demonstrate markedly enhanced production (0.61 +/- 0.09 units), but this does not increase significantly following endotoxin exposure (0.65 +/- 0.09 units). In contrast to macrophages from normal rat livers, macrophages recently recruited in the stilboestrol model demonstrate enhanced lysosomal enzyme production following endotoxin exposure. It is suggested that endotoxin, as well as other mediators of macrophage activation, may promote hepatic damage through this influence on newly recruited macrophages.
D000118:Acetylglucosaminidase / Q000378:metabolism*; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006099:Granuloma / Q000473:pathology; D006596:Hexosaminidases / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000201:enzymology*; D010587:Phagocytosis / Q000187:drug effects; D011425:Propionibacterium acnes; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D004054:Diethylstilbestrol; D006596:Hexosaminidases; D000118:Acetylglucosaminidase