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. 2007 Dec;83(3):296-300.
doi: 10.1016/j.yexmp.2007.09.001. Epub 2007 Oct 25.

M-30 and 4HNE are sequestered in different aggresomes in the same hepatocytes

Fataneh Amidi  1 , Barbara A French, David Chung, Charles H Halsted, Valentina Medici, Samuel W French
Affiliations

M-30 and 4HNE are sequestered in different aggresomes in the same hepatocytes

Fataneh Amidi et al. Exp Mol Pathol. 2007 Dec.

Abstract

M-30 and 4HNE adducts are two markers of active liver disease. M-30 is a serologic marker and 4HNE adducts are histologic markers. M-30 is a marker for apoptosis because it is a fragment of cytokeratin-18 left over from proteolysis by caspase 3. 4HNE is a marker of oxidative stress because it results from lipid peroxidation. Both markers are commonly found in nonalcoholic steatohepatitis and in alcoholic hepatitis. Liver biopsies from patients with steatohepatitis, 11 alcoholic and 11 non-alcoholics were stained for 4HNE and M-30. Almost all of the biopsies in both groups showed 4HNE- and M-30-positive aggresomes in hepatocytes. Mallory Denk bodies (MDB) stained variably positive for M-30, whereas 4HNE was present in aggresomes independent of MDBs. However, they were sometimes located in hepatocytes which also contained MDBs as shown by confocal microscopy of double stained biopsies. The results indicate that the formation of M-30 and 4HNE aggresomes occurs through different pathways of liver cell injury in both types of steatohepatitis.

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Figures

Fig 1
Fig 1
M-30 was present in MBs (arrows) (A-E) and in smaller aggresomes (C) in ASH patients’ liver biopsies compared to the control (F). Immunoperoxidase stain. ×260 (F), ×520 (B,E), ×780 (A, C, D).
Fig 2
Fig 2
M-30 was present in MDBs (arrows) in NASH patients’ liver biopsies (A). M-30 stained aggresomes were present in hepatocytes and macrophages (arrow heads) (A-D). Some livers were negative for any positive staining for M30 in the presence of steatosis (E) or steatohepatitis (F). Immunoperoxidase ×260 (B, C, D), ×520 (A, E, F).
Fig 3
Fig 3
4HNE positive aggresomes were found in hepatocytic cytoplasm of ASH biopsies (arrow) (A-C). MDBs stained negative with the 4HNE antibody where they were formed in ASH (A). This was confirmed by confocal microscopy (E-F). 4HNE aggresomes were also found in macrophages in secondary lysosomes (arrow head) A, (arrows) (C). ×218(B), ×436 (C-D), ×654 (A), ×1090 (E-G).
Fig 4
Fig 4
4HNE positive aggresomes were found in hepatocytic cytoplasm in the NASH patient biopsies (arrow heads) A and B and (arrow) C. MDBs failed to stain positive for 4HNE (arrow) B, D-F. Macrophages contained 4HNE positive secondary lysosomes in scarred areas (arrow head) C-D. Numerous MBs were found in the absence of 4HNE aggresomes in some cases (F). Immunocytochemistry stain (x130 F, ×520 A, B, E, ×780, C, D).
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