TIME-COURSE STUDY OF THE GOLGI-LYSOSOME REGION OF RAT HEPATOCYTES DURING EARLY ACUTE-PHASE RESPONSE TO INFLAMMATION

Background: In a previous study of the hepatocyte Golgi apparatus 24 h r following the induction of the acute phase response to inflammation, it was found that the predominant secretory content was a granulofila mentous material (GFM), rather than lipoprotein particles (LP) as in c ontrols (Thorne-Tjomsland and Jamieson, 1995, Anat. Rec., 241:439-450) . The present study aimed to determine when and how this switch occurs and to monitor the Golgi-lysosome region of hepatocytes in general du ring early inflammation. Methods: Rats were injected with turpentine o il as an inflammatory agent. At 1, 2, 6, 12, and 16 hr after turpentin e-injection (TI), the livers were prefixed by perfusion with cacodylat e-buffered glutaraldehyde, postfixed with ferrocyanide reduced osmium, and processed for thin section transmission electron microscopy. Resu lts: LP were processed at all time points between 1 and 16 hr post-TI, and at 1 and 2 hr post-TI, the Golgi stacks were engorged with LP and therefore apparently processed more of these particles than in contro ls. A GFM was processed at later time points, starting at 12 hr post-T I. At the two time points when LP and GFM were co-processed, these mat erials were frequently seen sorted from each other within the trans-sa ccule and/or the trans-Golgi network (TGN). At the level of the TGN, t hese materials were packaged into secretory vesicles which typically c ontained LP and/or GFM. Massive depletion of cytoplasmic glycogen was observed primarily at 1, 2, and 6 hr following TI. Concomitantly and t emporarily, glycogen accumulated within Golgi-associated lysosome-like bodies with extensive appendages. Conclusions: The switch in Golgi ap paratus secretory content from LP to GFM occurred at around 12 hr post -TI, but was not discrete. The initial appearance of the GFM coincided with the initial increase in the serum of hepatocyte-derived acute ph ase reactants (see review Schreiber et al., 1989, Ann. NY Acad. Sci., 557: 61-85). An additional and surprising finding of the present study was that significant changes occurred in the Golgi-lysosome region mu ch prior to the onset of acute phase reactant synthesis: 1 and 2 hr po st-TI, the Gels processed above-normal amounts of LP and Golgi-associa ted, lysosome-like bodies sequestered glycogen. (C) 1996 Wiley-Liss, I nc.