Histopathology 1992. 21, zyxwvutsr 335-344 Light microscopic and ultrastructural distribution of type VI collagen in human liver: alterations in chronic biliary disease z M.R.GRIFFITHS, M.SHEPHERD, R.FERRIER, D.SCHUPPAN*, 0.F.W.JAMESt zy & A. D .BURT$ University Department of Pathology, Western Infirmary, Glasgow, zyxwvu UK, *Division zyxw of Gastroenterology, Universitatsklinikum Steglitz, Freie Universitiit Berlin, Germany and tDepartment of Medicine (Geriatrics) and *Pathology, University of Newcastle upon Tyne, UK Date of zyxwvutsrq submission 11 March 1992 Accepted for publication 6 April 1992 GRIFFITHS M.R., SHEPHERD M., FERRIER R.. SCHUPPAN D., JAMES O.F.W. & BURT A.D. (1992) Histopathology 21, 335-344 Light microscopic and ultrastructural distribution of type VI collagen in human liver: alterations in chronic biliary disease 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 immuno- gold 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 111. 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 111 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 matrii and suggest that it may be synthesized by perisinusoidal (Ito) 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 observationsindicate that this 'minor' matrix component may play an important role in hepatic fibrogenesis. Keywords: type VI collagen, liver, immunohistochemical localization, immuno-electronmicroscopy Introduction The hepatic extracellular matrix is composed of four major classes of proteins: collagens, proteoglycans, glycoproteins and elastii1-2. Biochemical studies have defined the relative amounts of matrix components in normal liver and have established that most are' increased in hepatic fibrosis**2. The distribution of many of the major components within the liver has been delineated in immunohistochemical s t~dies~-~, some of Address for correspondence: Dr A.D.Burt, Division of Pathology. School of Pathological Sciences, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP. UK. which have dealt with their ultrastructural localization using immuno-electronmicroscopyb-l". These studies have not only provided information of importance to our understanding of the pathobiology of hepatic fibrosis but are relevant to the study of cell-matrii interactions in normal liver' l. The precise localization of many of the 'minor' extracellular matrix components is less well established. Although these proteins are present in lower amounts, some are known to be rapidly turned over and may increase substantially in fibrosis. Furthermore, some of these components may play important roles in modulat- ing hepatocyte function. One of the minor extracellular 335