Phagocytic function and metabolite production in thioacetamide-induced liver cirrhosis: a comparative study in perfused livers and cultured Kupffer cells.
OBJECTIVE
The aim of the study presented here was to evaluate the basal and stimulated phagocytic activities and the metabolite production of isolated perfused livers, and also the phagocytic capacity of cultured Kupffer cells from rats with macronodular cirrhosis.


METHODS
Rats were made cirrhotic by oral administration of thioacetamide. The phagocytic activity was assessed by the rate of removal of colloidal carbon. The Kupffer cells were prepared by a pronase/collagenase digestion method followed by elutriation.


RESULTS
The phagocytic activity and production of glucose, lactate and pyruvate were reduced in cirrhotic livers when calculated per g liver. Due to hyperplastic-regenerative processes the mass of the cirrhotic livers was markedly augmented so that the colloidal carbon uptake calculated per cirrhotic liver was not significantly different from the controls. Colloidal carbon-induced glucose release increased more markedly in the controls than in cirrhotic livers. Isoproterenol considerably stimulated phagocytosis and glucose production in controls, whereas the response was clearly reduced in cirrhotic livers when calculated either per g liver or per total liver weight. The cyclic AMP analogue elicited a marked glycogenolytic response in the controls, whereas there was only a slight increase in glucose production in cirrhotic livers. Phagocytosis of cirrhotic livers was only moderately stimulated by opsonized zymosan when compared with the controls. Freshly isolated Kupffer cells exhibited a reduced phagocytic activity. Stimulation by zymosan was observed only in cell suspensions of the controls. In contrast, Kupffer cells from cirrhotic livers did not differ from controls with respect to basal or zymosan-stimulated phagocytic activity after 48-h cultivation.


CONCLUSIONS
The stimulated phagocytic function was disturbed in perfused macronodular-cirrhotic livers as compared to controls. In contrast, 48-h cultured Kupffer cells from cirrhotic livers exhibited the same basal and stimulated phagocytic capacity as controls. The glucose release from perfused livers, initiated by stimulation of Kupffer cells or hepatocytes, was significantly reduced in cirrhotic livers. Therefore, we postulate an impaired intra- and/or intercellular signalling in macronodular-cirrhotic livers.
Petermann
H
H
Institute of Pathobiochemistry, Medical Faculty of Friedrich Schiller University Jena, Germany.
Heymann
S
S
Vogl
S
S
Dargel
R
R
D000818:Animals; D002244:Carbon / Q000493:pharmacokinetics; D003102:Colloids; D005260:Female; D005947:Glucose / Q000096:biosynthesis; D007545:Isoproterenol / Q000494:pharmacology; D007728:Kupffer Cells / Q000502:physiology*; D019344:Lactic Acid / Q000096:biosynthesis; D008099:Liver / Q000473:pathology / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D010586:Phagocytes / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D015054:Zymosan / Q000494:pharmacology
D003102:Colloids; D013853:Thioacetamide; D019344:Lactic Acid; D002244:Carbon; D019289:Pyruvic Acid; D015054:Zymosan; D005947:Glucose; D007545:Isoproterenol