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Localization of type III procollagen aminopeptide antigenicity in hepatocytes from cirrhotic human liver

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Immunolocalization of type III procollagen (pro III) in normal and cirrhotic human liver was studied using rabbit antiserum specific for bovine type III procollagen aminopeptide. The material examined was deparaffinized, trypsin-treated hepatic tissue sections from 28 autopsy cases, including 19 cirrhotic and 9 normal liver donors. Immunostaining, performed by the unlabeled peroxidase-antiperoxidase antibody technique demonstrated that extracellular matrices corresponding to perisinusoidal reticulin, collagen in periportal areas, and blood vessel walls were the common sites of pro III antigenicity in both normal and cirrhotic liver. Moreover, in the cirrhotic liver, the fibrous septa of pseudolobules, and cytoplasm of hepatocytes and sinusoidal cells were positive when stained for pro III peptide. The differential counts of pro III positive cells in cirrhotic liver, however, revealed that the average ratio of these hepatocytes to sinusoidal cells was 25 to 1, indicating complete dominance of hepatocytes with respect to stainability for pro III peptide compared to sinusoidal cells. In hepatocellular carcinomas co-existing with cirrhosis, neoplastic cells also displayed pro III antigenicity.

These data suggest that hepatocytes of cirrhotic liver and hepatocellular carcinoma cells play a significant role in type III collagen synthesis in vivo.

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  1. Becker U, Nowack H, Gay S, Timpl R (1976) Production and specificity of antibodies against the aminoterminal region in type III procollagen. Immunology 31:57–65

  2. Berman JJ, Foidart J-M (1980) Synthesis of collagen by rat liver epithelial cultures. ANN NY Acad Sci 349:153–164

  3. Gay S, Fiezek PP, Remberger K, Eder M, Kuhn K (1975) Liver cirrhosis: Immunofluorescence and biochemical studies demonstrate two types of collagen. Klin Wochenschr 53:205–208

  4. Gay S, Martin GR, Müller PK, Timpl R, Kühn K (1976) Simultaneous synthesis of types I and III collagen by fibroblasts in culture. Proc Natl Acad Sci USA 73:4037–4040

  5. Hata R, Ninomiya Y, Nagai Y, Tsukada Y (1980) Biosynthesis of interstitial types of collagen by albumin-producing rat liver parenchymal cell (hepatocyte) clone in culture. Biochemistry 19:169–176

  6. Hondo R, Kurata T, Sato S, Oda A, Aoyama Y (1982) Enzymatic treatment of formalin-fixed and paraffin-embedded specimens for detection of antigens of herpes simplex, varicella zoster and human cytomegalo viruses. Jp J Exp Med 52:17–25

  7. Huang S-N (1975) Immunohistochemical demonstration of hepatitis B core and surface antigens in paraffin sections. Lab Invest 33:88–95

  8. Igarashi S, Hatahara T, Funaki N (1983) Concentrations of aminoterminal peptide of type III procollagen in the sera of patients with various liver diseases with special reference to liver cancer. Acta Hepatologica Japonica 24:975–980

  9. Johnson KP, Swoveland PT, Emmons RW (1980) Diagnosis of rabies by immunofluorescence in trypsin-treated histologic sections. J Am Med Assoc 244:41–43

  10. Martinez-Hernandez A (1984) The hepatic extracellular matrix 1. Electron immunohistochemical studies in normal rat liver. Lab Invest 51:57–74

  11. Maruyama K, Okazaki I, Kobayashi T, Okuno F, Kamegaya K, Takagi S, Oda M, Ishii H, Tshuchida M (1984) Measurement of serum type III procollagen aminopeptide as a parameter of hepatic fibrosis. Acta Hepatologica Japonica 25:24–32

  12. Miettinen M, Franssila K, Lehto V-P, Paasivuo R, Virtanen I (1984) Expression of intermediate filament proteins in thyroid gland and thyroid tumors. Lab Invest 50:262–270

  13. Müller PK, Lemmen C, Gay S, Gauss V, Kühn K (1977) Immunochemical and biochemical study of collagen synthesis by chondrocytes in culture. Exp Cell Res 108:47–55

  14. Nakano H, Kawasaki T, Miyamura M, Fukuda Y, Imura H (1983) Serum levels of N-terminal type III procollagen peptide in normal subjects and comparison to hepatic fibrosis. Acta Hepatologica Japonica 24:1230–1234

  15. Nowack H, Gay S, Wick G, Becker U, Timpl R (1976) Preparation and use in immunohistology of antibodies specific for type I and type III collagen and procollagen. J Immunol Meth 12:117–127

  16. Qualman SJ, Keren DF (1979) Immunofluorescence of deparaffinized trypsin-treated renal tissues. Lab Invest 41:483–489

  17. Rohde H, Vargas L, Hahn E, Kalbfleisch H, Burguera M, Timpl R (1979) Radioimmunoassay for type III procollagen peptide and its application to human liver disease. Eur J Clin Invest 9:451–459

  18. Rojkind M, Martinez-Palmo A (1976) Increase in type I and type III collagens in human alcoholic liver cirrhosis. Proc Natl Acad Sci USA 73:539–543

  19. Saber MA, Zern MA, Shafritz DA (1983) Use of in situ hybridization to identify collagen and albumin mRNA in isolated rat hepatocytes. Proc Natl Acad Sci USA 80:4017–4020

  20. Sakakibara K, Suzuki T, Motoyama T, Watanabe H, Nagai Y (1982) Biosynthesis of an interstitial type of collagen by cloned human gastric carcinoma cells. Cancer Res 42:2019–2027

  21. Sakakibara K, Suzuki T, Tsukada Y, Nagai Y (1982) Distribution of type I collagen and basement membrane proteins in the culture of cloned epithelial liver cells. Cell Struct Funct 7:213–228

  22. Seyer JM, Hutcheson ET, Kang AH (1977) Collagen polymorphism in normal and cirrhotic human liver. J Clin Invest 59:241–248

  23. Smith BD, Niles R (1980) Characterization of collagen synthesized by normal and chemically transformed rat epithelial cell line. Biochemistry 19:1820–1825

  24. Thomas P, Said JW, Nash G, Banko-Schlegal S (1984) Profiles of keratin proteins in basal and squamous cell carcinomas of the skin. Lab Invest 50:36–41

  25. Timpl R, Wick G, Furthmayr H, Lapiere CM, Kühn K (1973) Immunochemical properties of procollagen from dermatosparactic calves. Eur J Biochem 32:584–591

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Correspondence to Kooko Sakakibara.

Additional information

The paper on this problem was read at the International Symposium on Pathobiology of Hepatic Fibrosis held in Matsue, Japan, on June 16, 1985

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Sakakibara, K., Igarashi, S. & Hatahara, T. Localization of type III procollagen aminopeptide antigenicity in hepatocytes from cirrhotic human liver. Vichows Archiv A Pathol Anat 408, 219–228 (1985). https://doi.org/10.1007/BF00707984

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Key words

  • Hepatic cirrhosis
  • Hepatocyte
  • Type III procollagen
  • Immunolocalization