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Changes in the cytokeratin intermediate filament cytoskeleton associated with Mallory body formation in mouse and
Y Katsuma1, S H Swierenga, U Khettry
1Department of Pathology, University of Ottawa, Ontario, Canada.
Abstract:
Mouse and human extracted liver tissue were examined by indirect immunofluorescent staining and transmission electron microscopy in order to study the alteration of cytokeratin intermediate filaments associated with Mallory body formation. Frozen sections of griseofulvin-fed mouse liver and human liver of primary biliary cirrhosis and primary sclerosing cholangitis were extracted by Triton X-100 and nuclease. Indirect immunofluorescent staining was performed by using anticow hoof keratin antibody for mouse liver and anti-human epidermal keratin antibody (AE1 and AE3) for human liver. Transmission electron microscopy was also performed on extracted and critical point-dried samples. The griseofulvin-fed mouse hepatoma cells showed four different types of altered staining pattern based on the indirect immunofluorescent staining of the cytoplasm and Mallory bodies: Type I--cytoplasm(+), Mallory body(-); Type II--cytoplasm(+), Mallory body(+); Type III--cytoplasm(-), Mallory body(+), and Type IV--cytoplasm(-), Mallory body(-). Types I and III were predominant, however, some hepatoma cells which contain Mallory bodies revealed bright cytoplasmic staining (Type II). The nuclear rims were strongly stained. In human liver, AE1 stained Mallory bodies and the bile duct epithelium intensely, but did not stain normal hepatocytes. AE3 mainly stained Mallory bodies and normal hepatocytes, but also stained bile duct epithelium weakly. Indirect immunofluorescent staining for human liver showed the same staining patterns as found in mouse liver, except that Type IV was not observed. Although many hepatocytes which contained Mallory bodies did not react with either of these two antibodies (Type III), some of the hepatocytes were stained, not only with AE3, but also with AE1 (Type II).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study investigates cytokeratin intermediate filament alterations during Mallory body formation in mouse and human liver tissues. Findings reveal distinct staining patterns associated with Mallory bodies, offering insights into liver disease pathogenesis.
Area of Science:
- Hepatology
- Cell Biology
- Pathology
Background:
- Mallory body formation is a hallmark of several liver diseases.
- Cytokeratin intermediate filaments are altered during hepatocellular injury.
- Understanding these alterations is crucial for diagnosing and managing liver conditions.
Purpose of the Study:
- To investigate the changes in cytokeratin intermediate filaments during Mallory body formation.
- To compare these changes in griseofulvin-induced mouse liver injury and human liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis).
Main Methods:
- Indirect immunofluorescent staining of liver tissue using specific keratin antibodies.
- Transmission electron microscopy to visualize ultrastructural changes.
- Analysis of staining patterns in relation to Mallory bodies and cellular compartments.
Main Results:
- Four distinct cytokeratin staining patterns were observed in mouse hepatoma cells associated with Mallory bodies.
- Human liver showed similar patterns, with AE1 intensely staining Mallory bodies and bile duct epithelium.
- Some hepatocytes with Mallory bodies exhibited positive staining with both AE1 and AE3 antibodies (Type II).
Conclusions:
- Cytokeratin intermediate filament alterations are closely associated with Mallory body formation in both experimental and human liver diseases.
- Specific keratin antibody staining patterns can help differentiate cellular changes in liver pathology.
- Further research into these alterations may provide diagnostic and prognostic markers for liver diseases.