Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1995 Jan;146(1):67–74.

Detection of apoptosis and expression of apoptosis-related proteins during human intrahepatic bile duct development.

T Terada 1, Y Nakanuma 1
PMCID: PMC1870763  PMID: 7531950

Abstract

We investigated apoptosis by nick end labeling and the expression of apoptosis-related proteins by immunohistochemistry in fetal development of human intrahepatic bile ducts and hepatocytes. During intrahepatic bile duct development, apoptosis was present at all stages, and its positive ratio was high in the remodeling ductal plate, moderate in the ductal plate, and relatively low in remodeled ducts. The cell proliferative activity as determined by proliferating cell nuclear antigen was also high in the remodeling ductal plate, and relatively low in the ductal plate and remodeled ducts. fas antigen and c-myc protein were constantly positive in the ductal plate, remodeling ductal plate and remodeled ducts. Bcl-2 protein was negative or faintly positive in the ductal plate and remodeling ductal plate, but was apparently positive in remodeled ducts. Lewisy as detected by the BM-1 antibody was present in the ductal plate, remodeling ductal plate, and remodeled ducts. p53 protein was not found in any cell types in the liver development. During hepatocyte development, many apoptotic and proliferating cell nuclear antigen-positive hepatocytes were noted. The developing hepatocytes expressed c-myc protein and fas antigen. Bcl-2 protein and Lewisy antigen were also weakly positive in the developing hepatocytes. These findings showed that balanced cell proliferation and apoptosis are involved in the normal development of intrahepatic bile ducts and hepatocytes, and suggest that c-myc protein, fas antigen, Bcl-2 protein, and Lewisy antigen modulate apoptosis of fetal intrahepatic biliary cells and hepatocytes, probably by stimulative (c-myc protein and fas and Lewisy antigens) or inhibitory (Bcl-2 protein) effects.

Full text

PDF
67

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Desmet V. J. Congenital diseases of intrahepatic bile ducts: variations on the theme "ductal plate malformation". Hepatology. 1992 Oct;16(4):1069–1083. doi: 10.1002/hep.1840160434. [DOI] [PubMed] [Google Scholar]
  2. Desmet V. J. Intrahepatic bile ducts under the lens. J Hepatol. 1985;1(5):545–559. doi: 10.1016/s0168-8278(85)80752-2. [DOI] [PubMed] [Google Scholar]
  3. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  4. Garcia R. L., Coltrera M. D., Gown A. M. Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues. Comparison with flow cytometric analysis. Am J Pathol. 1989 Apr;134(4):733–739. [PMC free article] [PubMed] [Google Scholar]
  5. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hiraishi K., Suzuki K., Hakomori S., Adachi M. Le(y) antigen expression is correlated with apoptosis (programmed cell death). Glycobiology. 1993 Aug;3(4):381–390. doi: 10.1093/glycob/3.4.381. [DOI] [PubMed] [Google Scholar]
  7. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  8. Hurle J. M. Cell death in developing systems. Methods Achiev Exp Pathol. 1988;13:55–86. [PubMed] [Google Scholar]
  9. Reed J. C. Bcl-2 and the regulation of programmed cell death. J Cell Biol. 1994 Jan;124(1-2):1–6. doi: 10.1083/jcb.124.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Shaw P., Bovey R., Tardy S., Sahli R., Sordat B., Costa J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495–4499. doi: 10.1073/pnas.89.10.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Shi S. R., Key M. E., Kalra K. L. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991 Jun;39(6):741–748. doi: 10.1177/39.6.1709656. [DOI] [PubMed] [Google Scholar]
  12. Terada T., Nakanuma Y. Development of human intrahepatic peribiliary glands. Histological, keratin immunohistochemical, and mucus histochemical analyses. Lab Invest. 1993 Mar;68(3):261–269. [PubMed] [Google Scholar]
  13. Terada T., Nakanuma Y. Development of human peribiliary capillary plexus: a lectin-histochemical and immunohistochemical study. Hepatology. 1993 Sep;18(3):529–536. [PubMed] [Google Scholar]
  14. Terada T., Nakanuma Y. Expression of tenascin, type IV collagen and laminin during human intrahepatic bile duct development and in intrahepatic cholangiocarcinoma. Histopathology. 1994 Aug;25(2):143–150. doi: 10.1111/j.1365-2559.1994.tb01570.x. [DOI] [PubMed] [Google Scholar]
  15. Terada T., Nakanuma Y. Profiles of expression of carbohydrate chain structures during human intrahepatic bile duct development and maturation: a lectin-histochemical and immunohistochemical study. Hepatology. 1994 Aug;20(2):388–397. [PubMed] [Google Scholar]
  16. Terada T., Ohta T., Nakanuma Y. Expression of transforming growth factor-alpha and its receptor during human liver development and maturation. Virchows Arch. 1994;424(6):669–675. doi: 10.1007/BF00195783. [DOI] [PubMed] [Google Scholar]
  17. Van Eyken P., Sciot R., Callea F., Van der Steen K., Moerman P., Desmet V. J. The development of the intrahepatic bile ducts in man: a keratin-immunohistochemical study. Hepatology. 1988 Nov-Dec;8(6):1586–1595. doi: 10.1002/hep.1840080619. [DOI] [PubMed] [Google Scholar]
  18. Vaux D. L., Cory S., Adams J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988 Sep 29;335(6189):440–442. doi: 10.1038/335440a0. [DOI] [PubMed] [Google Scholar]
  19. Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES