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A panel of 2 polyclonal and 7 monoclonal antibodies directed against cytokeratins was tested on cryostat and paraffin sections of 14 normal human liver biopsies using an immunoperoxidase procedure. The staining characteristics of hepatocytes and bile ducts are reported. On cryostat sections, monoclonal antibodies directed against individual cytokeratins no. 8 and no. 18 stained both bile ducts and hepatocytes, whereas monoclonals anti-cytokeratin no. 7 and no. 19 exclusively stained bile ducts. The potential use of these 4 monoclonal antibodies in liver histopathology is briefly discussed. Monoclonal antibody anti-type II cytokeratins and the polyclonal rabbit anti-human keratin stained only bile ducts on both cryostat and paraffin sections. Using monoclonal antibody CAM 5.2 on paraffin sections, both bile ducts and parenchyma were positive. An acinar gradient was apparent in that zone 1 hepatocytes were more intensely stained. Moreover, a rim of hepatocytes around terminal hepatic venules and adjacent to subhepatic veins showed more intense staining. The same gradient could be seen in some paraffin sections stained with the monoclonals anti-cytokeratin no. 18 and KL1, and the rabbit polyclonal anti-keratin "wide spectrum screening". The gradient is interpreted as reflecting quantitative differences in keratin content between hepatocytes. Polyclonal rabbit anti-human keratin is proposed as the most reliable antibody for identification of bile ducts in paraffin sections. The usefulness of reliable bile duct staining in several pathological conditions is emphasized.

Alpha-I-antitrypsin immunoreactivity was demonstrated by immunofluorescence in epithelial cells of the normal human small intestine. Its presence was also confirmed in biopsies of patients with Crohn's disease. Specific fluorescence was observed in only four out of 14 adult patients with coeliac disease. These results implicate the human small intestinal epithelium as a possible source of alpha-I-antitrypsin. The absence of positive cells may have implications in the aetiology of coeliac disease.

Various cholestatic liver diseases as well as regeneration after submassive necrosis are accompanied by a striking increase in the number of bile ductules. These reactive bile ductules are thought to arise either from proliferation of pre-existing bile ductules or bile ductule-related facultative stem cells, or from ductular metaplasia of hepatocytes. Recently, we found that reactive bile ductules display neuro-endocrine features, and speculated that the substance(s), produced in the neuro-endocrine granules, might play a role in their growth and/or differentiation through an autocrine or paracrine pathway. Parathyroid hormone-related peptide has been shown to be encoded by a growth factor-regulated gene that may play a role in cell growth and differentiation. We studied the immunohistochemical expression of this peptide in human liver, including three normal biopsies, 11 cases of cholestatic liver disease, six cases of focal nodular hyperplasia and three cases of regenerating liver. In regenerating liver, primary biliary cirrhosis, primary sclerosing cholangitis and partial or intermittent obstruction, the majority of reactive ductular cells expressing neuro-endocrine markers also expressed parathyroid hormone-related peptide. In focal nodular hyperplasia, a smaller number of bile ductular cells expressed the peptide. These findings suggest that parathyroid hormone-related peptide is localized in bile ductular cells and may indicate a role for this hormone in the growth and/or differentiation of human reactive bile ductules.