Abstract
Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern.
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barbatis C., Woods J., Morton J. A., Fleming K. A., McMichael A., McGee J. O. Immunohistochemical analysis of HLA (A, B, C) antigens in liver disease using a monoclonal antibody. Gut. 1981 Dec;22(12):985–991. doi: 10.1136/gut.22.12.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bianchi F. B., Biagini G., Ballardini G., Cenacchi G., Faccani A., Pisi E., Laschi R., Liotta L., Garbisa S. Basement membrane production by hepatocytes in chronic liver disease. Hepatology. 1984 Nov-Dec;4(6):1167–1172. doi: 10.1002/hep.1840040612. [DOI] [PubMed] [Google Scholar]
- Chia D., Terasaki P. I., Suyama N., Galton J., Hirota M., Katz D. Use of monoclonal antibodies to sialylated Lewisx and sialylated Lewisa for serological tests of cancer. Cancer Res. 1985 Jan;45(1):435–437. [PubMed] [Google Scholar]
- FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
- Feizi T. Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are onco-developmental antigens. Nature. 1985 Mar 7;314(6006):53–57. doi: 10.1038/314053a0. [DOI] [PubMed] [Google Scholar]
- Fleming K. A., McMichael A., Morton J. A., Woods J., McGee J. O. Distribution of HLA class 1 antigens in normal human tissue and in mammary cancer. J Clin Pathol. 1981 Jul;34(7):779–784. doi: 10.1136/jcp.34.7.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukuda M. Cell surface glycoconjugates as onco-differentiation markers in hematopoietic cells. Biochim Biophys Acta. 1985;780(2):119–150. doi: 10.1016/0304-419x(84)90002-7. [DOI] [PubMed] [Google Scholar]
- Fukushi Y., Nudelman E., Levery S. B., Hakomori S., Rauvala H. Novel fucolipids accumulating in human adenocarcinoma. III. A hybridoma antibody (FH6) defining a human cancer-associated difucoganglioside (VI3NeuAcV3III3Fuc2nLc6). J Biol Chem. 1984 Aug 25;259(16):10511–10517. [PubMed] [Google Scholar]
- Fukushima K., Hirota M., Terasaki P. I., Wakisaka A., Togashi H., Chia D., Suyama N., Fukushi Y., Nudelman E., Hakomori S. Characterization of sialosylated Lewisx as a new tumor-associated antigen. Cancer Res. 1984 Nov;44(11):5279–5285. [PubMed] [Google Scholar]
- Gomard E., Begue B., Sodoyer S., Maryanski J. L., Jordan B. R., Levy J. P. Murine cells expressing an HLA molecule are specifically lysed by HLA-restricted antiviral human T cells. Nature. 1986 Jan 9;319(6049):153–154. doi: 10.1038/319153a0. [DOI] [PubMed] [Google Scholar]
- Hakomori S. Glycosphingolipids in cellular interaction, differentiation, and oncogenesis. Annu Rev Biochem. 1981;50:733–764. doi: 10.1146/annurev.bi.50.070181.003505. [DOI] [PubMed] [Google Scholar]
- Hakomori S., Kannagi R. Glycosphingolipids as tumor-associated and differentiation markers. J Natl Cancer Inst. 1983 Aug;71(2):231–251. [PubMed] [Google Scholar]
- 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]
- Itzkowitz S. H., Yuan M., Fukushi Y., Palekar A., Phelps P. C., Shamsuddin A. M., Trump B. F., Hakomori S., Kim Y. S. Lewisx- and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues. Cancer Res. 1986 May;46(5):2627–2632. [PubMed] [Google Scholar]
- Kannagi R., Fukushi Y., Tachikawa T., Noda A., Shin S., Shigeta K., Hiraiwa N., Fukuda Y., Inamoto T., Hakomori S. Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing fucosyl or sialyl-fucosyl type 2 chain polylactosamine. Cancer Res. 1986 May;46(5):2619–2626. [PubMed] [Google Scholar]
- Kannagi R., Nudelman E., Levery S. B., Hakomori S. A series of human erythrocyte glycosphingolipids reacting to the monoclonal antibody directed to a developmentally regulated antigen SSEA-1. J Biol Chem. 1982 Dec 25;257(24):14865–14874. [PubMed] [Google Scholar]
- Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Ledeen R. W., Yu R. K. Gangliosides: structure, isolation, and analysis. Methods Enzymol. 1982;83:139–191. doi: 10.1016/0076-6879(82)83012-7. [DOI] [PubMed] [Google Scholar]
- Magnani J. L., Nilsson B., Brockhaus M., Zopf D., Steplewski Z., Koprowski H., Ginsburg V. A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. J Biol Chem. 1982 Dec 10;257(23):14365–14369. [PubMed] [Google Scholar]
- Magnani J. L., Smith D. F., Ginsburg V. Detection of gangliosides that bind cholera toxin: direct binding of 125I-labeled toxin to thin-layer chromatograms. Anal Biochem. 1980 Dec;109(2):399–402. doi: 10.1016/0003-2697(80)90667-3. [DOI] [PubMed] [Google Scholar]
- Martinez-Hernandez A. The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis. Lab Invest. 1985 Aug;53(2):166–186. [PubMed] [Google Scholar]
- Okada Y., Arima T., Hada H., Fukushima M., Watanabe J., Nagashima H. Human hepatocellular carcinoma is associated with quantitative and qualitative changes in glycolipids. Liver. 1985 Aug;5(4):226–235. doi: 10.1111/j.1600-0676.1985.tb00242.x. [DOI] [PubMed] [Google Scholar]
- Okada Y., Arima T., Togawa K., Nagashima H., Jinno K., Moriwaki S., Kunitomo T., Thurin J., Koprowski H. Neoexpression of ABH and Lewis blood group antigens in human hepatocellular carcinomas. J Natl Cancer Inst. 1987 Jan;78(1):19–28. doi: 10.1093/jnci/78.1.19. [DOI] [PubMed] [Google Scholar]
- Okada Y., Jinno K., Moriwaki S., Morichika S., Torigoe S., Arima T., Nagashima H., Koprowski H. Expression of ABH and Lewis blood group antigens in combined hepatocellular-cholangiocarcinoma. Possible evidence for the hepatocellular origin of combined hepatocellular-cholangiocarcinoma. Cancer. 1987 Aug 1;60(3):345–352. doi: 10.1002/1097-0142(19870801)60:3<345::aid-cncr2820600311>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
- Okada Y., Spiro R. G. Isolation and characterization of three major glycoproteins from thyroid plasma membranes. J Biol Chem. 1980 Sep 25;255(18):8865–8872. [PubMed] [Google Scholar]
- Spitalnik S. L., Schwartz J. F., Magnani J. L., Roberts D. D., Spitalnik P. F., Civin C. I., Ginsburg V. Anti-My-28, an antigranulocyte mouse monoclonal antibody, binds to a sugar sequence in lacto-N-neotetraose. Blood. 1985 Aug;66(2):319–326. [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van den Oord J. J., Desmet V. J. Verteilungsmuster der Histokompatibilitäts-Hauptantigene im normalen und pathologischen Lebergewebe. Leber Magen Darm. 1984 Nov;14(6):244–254. [PubMed] [Google Scholar]