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Toxicologic Pathology
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Partial Hepatectomy and Bile Duct Ligation in Rainbow Trout (Oncorhynchus mykiss): Histologic, Immunohistochemical and Enzyme Histochemical Characterization of Hepatic Regeneration and Biliary Hyperplasia

Mark S. Okihiro

Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, California 95616

David E. Hinton

Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, California 95616, msokihiro{at}ucdavis.edu

Hepatic regeneration following partial hepatectomy (PH) and biliary hyperplasia subsequent to bile duct ligation (BDL) were characterized in rainbow trout (Oncorhynchus mykiss) by light microscopy using routine and special (immunohistochemical and enzyme histochemical) stains. Both PH and BDL involved initial hypertrophy and hyperplasia of bile preductular epithelial cells (BPDECs). BPDECs are small oval cells that form junctional complexes with hepatocytes and bile ductular cells and are commonly found in hepatic tubules of teleost liver. Proliferating BPDECs transitioned through intermediate cell types before final differentiation into large basophilic hepatocytes (following PH) or biliary epithelial cells (after BDL). Normal BPDECs and hepatocytes were both negative for cytokeratin intermediate filaments in control fish when screened with the monoclonal antibody AE1/AE3. In contrast, hyperplastic BPDECs and their progeny (intermediate cells, immature hepatocytes, ductal epithelial cells) were all strongly cytokeratin positive. Cytokeratin expression was transient in newly differentiated hepatocytes (expression decreased as hepatocytes acquired characteristics consistent with full differentiation) but was permanent in biliary epithelial cells (expression was very strong in large mature ducts). BPDECs, intermediate cells, and immature ductal cells were also strongly positive for alkaline phosphatase following BDL. Chronology of histologic events and cytokeratin and enzyme expression all support the hypothesis that BPDECs possess the capacity to differentiate into either hepatocytes or biliary epithelial cells. Thus, BPDECs may be the teleost equivalent of a bipolar hepatic stem cell in mammals.

Key Words: Liver • histopathology • cytokeratin • stem cell • fish

References

  • Alison M., Golding M., Lalani EN, Nagy P., Thorgeirsson S., Sarraf C. (1997). Wholesale hepatocytic differentiation in the rat from ductal oval cells and the progeny of biliary stem cells. J Hepatol 26: 343-352.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Banks WJ (1993). Digestive system. In: Applied Veterinary Histology. Waverly Press, Baltimore, Maryland, pp 373-419.
  • Barka T., Anderson PJ (1962). Histochemical methods for acid phosphatase using hexa zonium pararosaniline as a coupler. J Histochem Cytochem 10: 741-753.[Web of Science]
  • Bucher Nlr, Malt RA ( 1971). Regeneration of the Liver and Kidney. Little, Brown and Co, Boston.
  • Bunton TE (1993). The immunohistochemistry of cytokeratin in fish tissues. Vet Pathol 30: 418-425.[Abstract]
  • Burstone MS, Weisburger EK (1961). New diazonium compounds as coupling agents in the detection of phosphatases. J Histochem Cytochem 9: 301-303.[Abstract]
  • Chou ST, Gibson JB (1972). A comparative histochemical study of rat livers in alpha-naphthyl-isothiocyanate (ANIT) and DL-ethionine intoxication. J Pathol 108: 73-83.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cooper D., Schermer A., Sun TT ( 1985). Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: Strategies, applications, and limitations. Lab Invest 52: 243-256.[Web of Science][Medline] [Order article via Infotrieve]
  • Crosby HA, Hubscher S., Fabris L., Joplin R., Sell S., Kelly D., Strain AJ (1998). Immunolocalization of putative human liver progenitor cells in live patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6. Am J Pathol 152: 771-779.[Abstract]
  • Crosby HA, Hubscher SG, Joplin RE, Kelly DA, Strain AJ (1998). Immunolocalization of OV-6, a putative progenitor cell marker in human fetal and diseased pediatric liver. Hepatology 28: 980-985.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Engelhardt NV, Baranov VN, Zareva MN, Goussov AI (1984). U1-trastructural localization of {alpha}-fetoprotein (AFP) in regenerating mouse liver poisoned with CCl 4: Reexpression of AFP in differentiated hepatocytes. Histochemistry 80: 401-407.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Evarts R., Nagy P., Marsden E., Thorgeirsson S. (1987). A precursorproduct relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis 8: 1737-1740.[Abstract/Free Full Text]
  • Evarts R., Nagy P., Nakatsukasa H., Marsden E., Thorgeirsson S. (1989). In vivo differentiation of rat liver oval cells into hepatocytes. Cancer Res 49: 1541-1547.[Abstract/Free Full Text]
  • Faa G., Van Eyken P, Roskams T., Miyazaki H., Serreli S., Ambu R., Desmet VJ (1998). Expression of cytokeratin 20 in developing rat liver and in experimental models of ductular and oval cell proliferation. J Hepatol 29: 628-633.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Farber E. (1956). Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylaminofluorene, and 3'-methyl-4-dimethylaminoazobenzene. Cancer Res 16: 142-149.[Free Full Text]
  • Fishback FC (1929). A morphologic study of regeneration of the liver after partial removal. Arch Pathol 7: 955-977.[Web of Science]
  • Franke WW, Denk H., Kalt R., Schmid E. (1981). Biochemical and immunological identification of cytokeratin proteins present in hepatocytes of mammalian liver tissue. Exp Cell Res 131: 299-318.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Fuchs E. (1995). Keratins and the skin. Annu Rev Cell Dev Biol 11: 123-153.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Fuchs EV, Marchuk D. (1983). Type I and type II keratins have evolved from lower eukaryotes to form the epidermal intermediate filaments in mammalian skin. Proc Natl Acad Sci USA 80: 5857-5861.[Abstract/Free Full Text]
  • Fuchs E., Weber K. (1994). Intermediate filaments: Structure, dynamics, function, and disease. Annu Rev Biochem 63: 345-382.[Web of Science][Medline] [Order article via Infotrieve]
  • Germain L., Blouin M., Marceau N. (1988). Biliary epithelial and hepatocytic cell lineage relationships in embryonic rat liver as determined by the differential expression of cytokeratins, alpha-fetoprotein, albumin, and cell-surface exposed components. Cancer Res 48: 4909-4918.[Abstract/Free Full Text]
  • Germain L., Goyette R., Marceau N. (1985). Differential cytokeratin and alpha-fetoprotein expression in morphologically distinct epithelial cells emerging at the early stages of rat hepatocarcinogenesis. Cancer Res 45: 673-681.[Abstract/Free Full Text]
  • Hampton JA, Lantz RC, Goldblatt PJ, Lauren DJ, Hinton DE (1988). Functional units in rainbow trout (Salmo gairdneri, Richardson) liver: II. The biliary system. Anat Rec 221: 619-634.[CrossRef][Medline] [Order article via Infotrieve]
  • Hampton JA, Lantz RC, Hinton DE (1989). Functional units in rainbow trout (Salmo gairdneri, Richarson) liver: III. Morphometric analysis of parenchyma, stroma, and component cell types. Am J Anat 185: 58-73.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hampton JA, McCuskey PA, McCuskey RS, Hinton DE (1985). Functional units in rainbow trout (Salmo gairdneri) liver: I. Arrangement and histochemical properties of hepatocytes. Anat Rec 213: 166-175.[CrossRef][Medline] [Order article via Infotrieve]
  • Hendricks JD, Meyers TR, Shelton DW (1984). Histologic progression of hepatic neoplasia in rainbow trout (Salmo gairdneri). Natl Cancer Inst Monogr 65: 321-336.[Medline] [Order article via Infotrieve]
  • Hinton DE (2000). Structural considerations in teleost hepatocarcinogenesis: Gross and microscopic features including architecture, specific cell types and focal lesions. In: Atlas of Neoplasms and Related Disorders, Dawe CJ (ed). Academic Press, New York (in press).
  • Hinton DE, Couch J. (1997). Architectural pattern, tissue and cellular morphology in livers of fishes: Relationship to experimentally-induced neoplastic responses. In: Fish Ecotoxicology. Birkhäuser, Basel, Switzerland, pp 141-164.
  • Inaoka Y. (1969). Significance of the so-called oval cell proliferation during azo-dye hepatocarcinogenesis. Gann 58: 355-366.
  • Kalengayi MM, Desmet VJ (1976). Histochemical patterns of two oncofetal markers, gamma-glutamyl transpeptidase and alpha-1-fetoprotein during aflatoxin hepatocarcinogenesis in the rat. In: Liver Cancer, Shanmugaratnam K, Nambiar R, Tan KK, Chan LK (eds). Stanford Press, Singapore, pp 198-200.
  • Koukoulis G., Rayner A., Tan KC, Williams R., Portmen B. (1992). Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining. J Pathol 166: 359-366.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lai YS, Thung SN, Gerber MA, Chen ML, Schaffner F. (1989). Expressions of cytokeratins in normal and diseased livers and in primary liver carcinomas. Arch Pathol Lab Med 113: 134-138.[Web of Science][Medline] [Order article via Infotrieve]
  • Lee BC, Hendricks JD, Bailey GS (1989). Metaplastic pancreatic cells in liver tumors induced by diethylnitrosamine. Exp Mol Pathol 50: 104-113.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lemire JM, Shiojiri N., Fausto N. (1991). Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine. Am J Pathol 51: 2611-2620.
  • Listrom MB, Dalton LW (1987). Comparison of keratin monoclonal antibodies. Am J Clin Pathol 88: 297-301.[Web of Science][Medline] [Order article via Infotrieve]
  • Lojda Z. (1965). Remarks on histochemical detection of dehydrogenases. II. Intracellular localization. Folia Morphol ( Prague) 13: 84-96.
  • Marceau N., Blouin M., Germain L., Noel M. ( 1989). Role of different epithelial cell types in liver otogenesis, regeneration and neoplasia. In Vitro Cell Dev Biol 25: 336-341.[Web of Science][Medline] [Order article via Infotrieve]
  • Markl J., Franke WW (1988). Localization of cytokeratins in tissues of the rainbow trout: Fundamental differences in expression pattern between fish and higher vertebrates. Differentiation 39: 97-122.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Markl J., Schechter N. (1998). Fish intermediate filament proteins in structure, evolution, and function. Subcell Biochem 31: 1-33.[Medline] [Order article via Infotrieve]
  • Markl J., Winter S., Franke WW (1989). The catalog and the expression complexity of cytokeratins in a lower vertebrate: Biochemical identification of cytokeratins in a teleost fish, the rainbow trout. Eur J Cell Biol 50: 1-16.[Web of Science]
  • McLean MR, Reese KR (1958). Hyperplasia of bile ducts induced by alpha-naphthyl-iso-thiocyanate: Experimental biliary cirrhosis free from biliary obstruction. J Pathol Bacteriol 76: 175-188.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Meyers TR, Hendricks JD (1985). Histopathology. In: Fundamentals of Aquatic Toxicology, Rand GM, Petrocelli SR (eds). Hemisphere Publishing, Washington, DC, pp 283-331.
  • Moll R., Franke WW, Schiller DL, Geiger B., Krepler, R. (1982). The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors, and cultured cells. Cell 31: 11-24.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ostrander GK, Blair JB, Stark BA, Marley GM, Bales WD, Veltri RW, Hinton DE, Okihiro MS, Ortego LS, Haweekins WE (1995). Long-term primary culture of epithelial cells from rainbow trout (Oncorhynchus mykiss) liver. In Vitro Cell Dev Biol 31: 367-378.[CrossRef][Web of Science]
  • Okihiro MS (1996). Regenerative, hyperplastic, and neoplastic hepatic growth in medaka (Oryzias latipes) and rainbow trout (Oncorhynchus mykiss): An investigation of the role of the bipolar hepatic stem cell. University of California, Davis, PhD thesis.
  • Petropoulos CJ, Yaswen P., Panzica M., Fausto N. (1985). Cell lineages in liver car cinogenesis: Possible clues from studies of the distribution of {alpha}-fetoprotein RNA sequences in cell populations isolated from normal, regenerating and preneoplastic rat livers. Cancer Res 45: 5762-5768.[Abstract/Free Full Text]
  • Pretlow TP, Crane RW, Goehring PL, Lapinsky AS, Pretlow TG (1987). Examination of enzyme altered foci with gamma-glutamyl transpeptidase, aldehyde dehydrogenase, glucose-6-phosphate dehydrogenase and other markers in methacrylate embedded liver. Lab Invest 56: 96-100.[Web of Science][Medline] [Order article via Infotrieve]
  • Rabes HM, Wirsching R., Tuczek HV, Iseler G. (1976). Analysis of cell cycle compartments of hepatocytes after partial hepatectomy. Cell Tissue Kinet 9: 517-532.[Web of Science][Medline] [Order article via Infotrieve]
  • Reider H., Teutsch HF, Sasse D. (1978). NADP-dependent dehydrogenases in rat liver parenchyma. I. Methodological studies on the qualitative histochemistry of G6PDH, 6PGDH, malic enzyme, and ICDH. Histochemistry 56: 283-298.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Richards WL, Tsukada Y., Potter VR (1982). {gamma}-Glutamyl transpeptidase and {alpha}-fetoprotein expression during {alpha}-naphthylisothiocyanate-induced hepatotoxicity in rats. Cancer Res 42: 5133-5138.[Abstract/Free Full Text]
  • Rocha E., Monteiro Raf, Pereira CA (1997). Liver of the brown trout Salmo trutta (Teleostei, Salmonidae): A stereological study at light and electron microscopic levels. Anat Rec 247: 317-328.[CrossRef][Medline] [Order article via Infotrieve]
  • Roskams T., De Voss R., Desmet V. (1996). 'Undifferentiated progenitor cells' in nodular hyperplasia of the liver. Histopathology 28: 291-299.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Rutenberg AM, Kim H., Fishbein JW. Hanker LS, Wasserkrug HI, Seligman AM (1969). Histochemical and ultrastructural demonstration of gamma-glutamyl transpeptidase activity. J Histochem Cytochem 17: 517-526.[Abstract]
  • Sanz A., Garcia M., Cardenete G. Zamora S (1982). Hepatectomy in rainbow trout (Salmo gairdnerii). A preliminary study. Comp Biochem Physiol 71: 329-332.[CrossRef][Medline] [Order article via Infotrieve]
  • Sanz A., Hidalgo MC, Cardenete G., Garcia M., De La Higuera M. (1986). Some functional consequences of partial hepatectomy in rainbow trout (Salmo gairdnerii). Comp Biochem Physiol 83: 213-215.[Medline] [Order article via Infotrieve]
  • Sell S., Pierce GB (1994). Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest 70: 6-22.[Web of Science][Medline] [Order article via Infotrieve]
  • Sells MA, Katyal SL, Shinozuka H., Estes LW, Sell S., Lombardi B. (1981). Isolation of oval cells and transitional cells from the livers of rats fed the carcinogen DL-ethionine. J Natl Cancer Inst 66: 355-362.[Web of Science][Medline] [Order article via Infotrieve]
  • Sirica AE, Cihla HP (1984). Isolation and partial characterization of oval and hyperplastic bile ductular cell-enriched populations from the livers of carcinogen and noncarcinogen-treated rats. Cancer Res 44: 3454-3466.[Abstract/Free Full Text]
  • Steiner JW, Carruthers JS (1961). Studies on the fine structure of the terminal branches of the biliary tree. I. The morphology of normal bile preductules (ducts of Hering) and bile ductules. Am J Pathol 38: 639-661.[Web of Science]
  • Steiner JW, Carruthers JS (1962). Experimental extrahepatic biliary obstruction. Some aspects of the fine structural changes of bile ductules and pre-ductules (ducts of Hering). Am J Pathol 40: 253-270.[Web of Science][Medline] [Order article via Infotrieve]
  • Steiner JW, Carruthers JS (1963). Electron microscopy of hyperplastic ductular cells in {alpha}-naphthyl isothiocyanate-induced cirrhosis. Lab Invest 12: 471-498.[Web of Science][Medline] [Order article via Infotrieve]
  • Teh SJ, Hinton DE (1993). Detection of enzyme histochemical markers of hepatic preneoplasia and neoplasia in medaka (Oryzias latipes). Aquat Toxicol 24: 163-182.[CrossRef][Web of Science]
  • Tournier I., Legres L., Schoevaert D., Feldman G., Bernuau D. (1988). Cellular analysis of {alpha}-fetoprotein gene activation during carbon tetrachloride and D-galactosamine-induced acute liver injury in rats. Lab Invest 59: 657-665.[Web of Science][Medline] [Order article via Infotrieve]
  • Tseng Slg, Jarvinen MJ, Nelson WG, Huang JW, Woodcock-Mitchel J., Sun TT ( 1982). Correlation of specific keratins with different types of epithelial differentiation: Monoclonal antibody studies. Cell 30: 361-372.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Wilson JW, Leduc EM (1958). Role of cholangioles in restoration of the liver of the mouse after dietary injury. J Pathol Bacteriol. 76: 441-449.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Yaswen P., Hayner NT, Fausto N. (1984). Isolation of oval cells by centrifugal elutriation and comparison with other cell types purified from normal and preneoplastic livers. Cancer Res 44: 324-331.[Abstract/Free Full Text]
  • Yaswen P., Thompson NL, Fausto N. (1985). Oncodevelopmental expression of rat placental alkaline phosphatase. Detection in oval cells during liver carcinogenesis. Am J Pathol 121: 505-513.[Abstract]

Toxicologic Pathology, Vol. 28, No. 2, 342-356 (2000)
DOI: 10.1177/019262330002800215
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