PHAGOCYTIC FUNCTION AND METABOLITE PRODUCTION IN THIOACETAMIDE-INDUCED LIVER-CIRRHOSIS - A COMPARATIVE-STUDY IN PERFUSED LIVERS AND CULTURED KUPFFER CELLS

Background/Aims: The aim of the study presented here was to evaluate t he basal and stimulated phagocytic activities and the metabolite produ ction 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. Th e phagocytic activity was assessed by the rate of removal of colloidal carbon. The Kupffer cells were prepared by a pronase/collagenase dige stion method followed by elutriation. Results: The phagocytic activity and production of glucose, lactate and pyruvate were reduced in cirrh otic livers when calculated per g liver. Due to hyperplastic-regenerat ive 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-induc ed glucose release increased more markedly in the controls than in cir rhotic livers. Isoproterenol considerably stimulated phagocytosis and glucose production in controls, whereas the response was clearly reduc ed in cirrhotic livers when calculated either per g liver or per total liver weight. The cyclic AMP analogue elicited a marked glycogenolyti c response in the controls, whereas there was only a slight increase i n glucose production in cirrhotic livers. Phagocytosis of cirrhotic li vers 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 cirrhoti c livers did not differ from controls with respect to basal or zymosan -stimulated phagocytic activity after 48-h cultivation. Conclusion: Th e stimulated phagocytic function was disturbed in perfused macronodula r-cirrhotic livers as compared to controls. In contrast, 48-h cultured Kupffer cells from cirrhotic livers exhibited the same basal and stim ulated phagocytic capacity as controls. The glucose release from perfu sed 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-ci rrhotic livers.