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Relationship of Mallory bodies to intermediate filaments in hepatocytes. A scanning electron microscopy study
Abstract:
Livers from 12 mice fed griseofulvin for 4 to 6 months were perfused in situ with a detergent solution to extract lipid membranes leaving the cytoskeleton intact. Seven control mice were similarly studied. After 30 to 120 minutes perfusion, liver samples were examined by scanning electron microscopy and transmission electron microscopy. By light microscopy, Mallory bodies (MBs) were observed in pericentral hepatocytes. These were confirmed by transmission electron microscopy. Intermediate filaments (IFs) were observed in close apposition to MBs. Numerous IFs were seen throughout the cytoplasm. The 3-dimensional organization of the cytoskeleton and MBs were clearly visualized by scanning electron microscopy. The IFs were disorganized in the hepatocytes and formed small MBs in griseofulvin-treated mice. In the case of hepatocytes containing large MBs, there was an apparent decrease in the concentration of IFs. Transition forms of dense networks of IFs between the normal cytoskeleton and the MBs were noted in the cytoplasm between small MBs and the nucleus and also at the cell border. The IFs connected to the nucleus and invaded the MBs. The MBs appeared to form as a result of condensation or collapse of the IFs.
Insights
Griseofulvin treatment disrupts hepatocyte intermediate filaments (IFs), causing them to aggregate into Mallory bodies (MBs). This study visualizes the cytoskeleton
Area of Science:
- Hepatology
- Cell Biology
- Toxicology
Background:
- Mallory bodies (MBs) are protein aggregates found in hepatocytes, often associated with liver injury.
- The role of the cytoskeleton, particularly intermediate filaments (IFs), in MB formation is not fully understood.
Purpose of the Study:
- To investigate the relationship between griseofulvin-induced liver injury and the structural changes in hepatocyte intermediate filaments (IFs).
- To elucidate the role of IFs in the formation and organization of Mallory bodies (MBs).
Main Methods:
- Livers from griseofulvin-treated and control mice were perfused and examined using light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM).
- SEM was utilized to visualize the 3D organization of the cytoskeleton and MBs.
Main Results:
- Griseofulvin-treated mice exhibited Mallory bodies (MBs) in pericentral hepatocytes.
- Intermediate filaments (IFs) were found in close association with MBs, showing disorganization and condensation into small MBs.
- Hepatocytes with large MBs showed decreased IF concentration, with transition forms suggesting IFs contribute to MB formation.
Conclusions:
- Mallory bodies (MBs) appear to form through the condensation or collapse of disorganized intermediate filaments (IFs) in hepatocytes.
- The study provides new insights into the cytoskeletal basis of drug-induced liver injury and MB pathogenesis.