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Light microscopic and ultrastructural distribution of type VI collagen in human liver: alterations in chronic biliary
M R Griffiths1, M Shepherd, R Ferrier
1University Department of Pathology, Western Infirmary, Glasgow, UK.
Insights
Type VI collagen is abundant in the normal human liver extracellular matrix, particularly in perisinusoidal cells. This collagen also accumulates in fibrotic liver disease, suggesting a role in hepatic fibrogenesis.
Area of Science:
- Hepatic histology and extracellular matrix research.
- Cellular and molecular biology of collagen.
- Pathology of liver fibrosis.
Background:
- Type VI collagen is a minor component of the extracellular matrix.
- Its distribution and role in normal and diseased liver are not fully understood.
Purpose of the Study:
- To investigate the distribution of type VI collagen in normal human liver.
- To compare its distribution with type III collagen.
- To explore the role of type VI collagen in primary biliary cirrhosis.
Main Methods:
- Immunohistochemistry (peroxidase-antiperoxidase method) for light microscopy.
- Immunogold labeling for ultrastructural localization.
- Analysis of normal liver from transplant donors and cirrhotic liver biopsy samples.
Main Results:
- Type VI collagen is present in Glisson's capsule, portal tracts, and the space of Disse, with heterogeneous perisinusoidal staining.
- It is found on amorphous material between collagen fibrils and intracellularly in perisinusoidal (Ito) cells.
- Type III collagen also localizes to the space of Disse but without intra-acinar heterogeneity.
- Intense type VI collagen staining surrounds bile ductules in fibrotic septa of cirrhotic livers.
Conclusions:
- Type VI collagen is a ubiquitous component of the normal hepatic extracellular matrix, potentially synthesized by perisinusoidal (Ito) cells.
- Its increased presence in fibrotic liver suggests a significant role in hepatic fibrogenesis.
Abstract:
We have investigated the distribution of type VI collagen in normal human liver obtained from cadaveric renal transplant donors, using a peroxidase-antiperoxidase method for light microscopic visualization, and an immunogold labelling method for ultrastructural localization. The distribution was compared with that of the more abundant interstitial collagen type III, using antibodies to amino terminal procollagen type III. Staining for type VI collagen was identified in Glisson's capsule, in portal tract stroma and within the space of Disse. Perisinusoidal staining showed intra-acinar heterogeneity with the intensity in acinar zones 2 and 3 being greater than in zone 1. Type III collagen was also found in the space of Disse although no significant intra-acinar variation in staining intensity was noted. Immuno-gold labelling for type VI collagen was demonstrated on amorphous or microfilamentous material lying between, and occasionally appearing to interconnect, cross-striated collagen fibrils, whereas labelling for amino terminal procollagen type III was exclusively on fibrils. Intracellular staining for type VI collagen was noted in perisinusoidal (lto) cells. These results confirm that type VI collagen is a ubiquitous constituent of the normal hepatic extracellular matrix and suggest that it may be synthesized by perisinusoidal (lto) cells. The distribution of type VI collagen was also studied in biopsy material from patients with different histological stages of primary biliary cirrhosis. Intense staining was noted around proliferating bile ductules within developing fibrous septa and in established septa of cirrhotic liver. These observations indicate that this 'minor' matrix component may play an important role in hepatic fibrogenesis.