MACROPHAGES FROM RAT LIVERS WITH MICRONODULAR AND MACRONODULAR CIRRHOSIS DIFFER WITH RESPECT TO MEDIATOR RELEASE AND DNA-SYNTHESIS

Background/Aims: Liver macrophages play an essential role in necro-inf lammatory liver damage which leads to fibrosis and cirrhosis. The aim of the present study was to compare the mediator release and the DNA s ynthesis of macrophages at an early and at a later stage of liver cirr hosis induced by thioacetamide. Methods: Liver macrophages were isolat ed by an enzymic digestion method, followed by elutriation. The releas e of reactive oxygen species and cytokines, and the synthesis of DNA w ere measured in cultivated cells. Results: The vitality of isolated ma crophages from cirrhotic livers was always higher than 98%. The total yield of macrophages was less in micronodular cirrhotic livers and was markedly higher in macronodular cirrhotic livers when compared with a ge-matched controls. The cellular granules measured by sideward light scattering showed a shift to larger sizes in macrophages from micronod ular cirrhotic livers when compared with the controls and the other ex perimental group. Macrophages from both cirrhosis groups exhibited a m arkedly higher unstimulated and lipopolysaccharide-stimulated IL-6 pro duction than the controls. The release of TNF-alpha did not differ bet ween controls and the experimental groups. Macrophages from macronodul ar cirrhotic livers produced higher amounts of nitric oxide but less s uperoxide anion radicals than the controls. DNA synthesis was 10-12-fo ld and 3-10-fold higher in macrophages from micronodular and macronodu lar cirrhotic livers, respectively, when compared with the age-matched controls. Conclusions: The data presented provide evidence that it is possible to isolate and to cultivate macrophages from livers with hig h yield and vitality at different stages of cirrhogenesis. Our results clearly demonstrate functional differences between macrophages from l ivers with micro- or macronodular cirrhosis; this finding may be impor tant for the pathogenesis or perpetuation of the cirrhogenetic process .