Summary
There is now substantial evidence that perisinusoidal (Ito or fat-storing) cells are the principal source of extracellular matrix proteins during hepatic fibrogenesis. In rat liver these cells express the intermediate fiament protein desmin; this is now widely used as an immunohistochemical marker for these cells. It has been shown that in experimental models of acute and chronic liver injury there is an increase in the number of desmin-positive perisinusoidal cells prior to the deposition of matrix proteins; however, these studies have failed to establish whether local proliferation is involved in this expansion of the desmin-positive perisinusoidal cell population.
In order to investigate the kinetics of the perisinusoidal cell response, we have developed a novel double-labelling immunohistochemical technique for the simultaneous demonstration of desmin and incorporated bromodeoxyuridine in proliferating perisinusoidal cells in sections of fixed paraffiin-embedded rat liver. Application of this technique to a model of acute liver injury (single dose carbon tetrachloride by gavage) has shown that expansion of the perisinusoidal cell population is contributed to by local proliferation, with a labelling index of 18.7% 2 days following injury.
Similar content being viewed by others
References
Arenson, D. M., Friedman, S. L. &Bissell, D. M. (1988) Formation of extracellular matrix in normal rat liver: lipocytes as a major source of proteoglycan.Gastroenterology 95, 441–7.
Aterman, K. (1986) The parasinusoidal cells of the liver: a historical account.Histochem. J. 18, 279–305.
Bioulac-Sage, P., Lafon, M. E., Le Bail, B. &Balabaud, C. (1988)Sinusoids in Human Liver: Health and Disease (edited byBioulac-Sage, P. &Balabaud, C.) pp. 39–62. The Kupffer Cell Foundation, Rijswijk, The Netherlands.
Bissell, D. M., Friedman, S. L., Maher, J. J. &Roll, F. J. (1990) Connective tissue biology and hepatic fibrosis: report of a conference.Hepatology 11, 488–98.
Burt, A. D., Robertson, J. L., Heir, J. &Macsween, R. N. M. (1986) Desmin-containing stellate cells in rat liver, distribution in normal animals and response to experimental acute liver injury.J. Pathol. 150, 29–35.
Friedman, S. L., Roll, F. J., Boyles, J. &Bissell, D. M. (1985) Hepatic lipocytes: the principal collagen-producing cells of normal rat liver.Proc. Natl Acad. Sci. USA 82, 8681–5.
Gratzner, H. G. (1982) Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication.Science 218, 474–5.
Gressner, A. M. &Bachem, M. G. (1990) Cellular sources of noncollagenous matrix proteins: role of fat-storing cells in fibrogenesis.Sem. Liver Dis. 10, 30–46.
Hall, P. A. &Levison, D. A. (1990) Review: assessment of cell proliferation in histological material.J. Clin. Pathol. 43, 184–92.
Hayashi, Y., Koike, M., Matsutani, M. &Hoshino, T. (1988) Effects of fixation time and enzymatic digestion on immunohistochemical demonstration of bromodeoxyuridine in formalin-fixed paraffin-embedded tissue.J. Histochem. Cytochem. 36, 511–4.
Jézéquel, A. M., Mancini, R., Rinaldesi, M. L., Ballardini, G., Fallani, M., Bianchi, F. &Orlandi, F. (1989) Dimethylnitrosamine-induced cirrhosis: evidence for an immunological mechanism.J. Hepatol. 8, 42–52.
Jonker, A. M., Dijkhuis, F. W. J., Kroese, F. G. M., Hardonk, M. J. &Groud, J. (1990) Immunopathology of acute galactosamine hepatitis in rats.Hepatology 11, 622–7.
Magaud, J.-P., Sargent, I., Clarke, P. J., Ffrench, M., Rimokh R. &Mason, D. Y. (1989) Double immunocytochemical labelling of cell and tissue samples with monoclonal anti-bromodeoxyuridine.J. Histochem. Cytochem. 37, 1517–27.
McGee, J. O'd. &Patrick R. S. (1972) The role of perisinusoidal cells in hepatic fibrogenesis, an electron microscopic study of acute carbon tetrachloride liver injury.Lab. Invest. 26, 429–40.
Robertson, H., Wheeler, J. &Morley, A. R. (1990)In vivo bromodeoxyuridine incorporation in normal mouse kidney: immunohistochemical detection and measurement of labelling indices.Histochem. J. 22, 209–14.
Schutte B., Reynders M. J., Bosman F. T. &Blijham G. H. (1987) Studies with anti-bromodeoxyuridine antibodies: II. Simultaneous immunocytochemical detection of antigen expression and DNA synthesis byin vivo labelling of mouse intestinal mucosa.J. Histochem. Cytochem. 35, 371–4.
Tanaka, Y., Mak, K. M. &Lieber, C. S. (1990) Immunohistochemical detection of proliferating lipocytes in regenerating rat liver.J. Pathol. 160, 129–34.
Wisse, E., Geerts, A., Bouwens, L., van Bossuyt, H., Vander-Kerken, K. &Van Goethem, F. (1989)Cell of the Hepatic Sinusoid (edited byWisse, E., Knook, D. L. &Decker, K.) Vol 2. pp. 1–9. The Kupffer Cell Foundation, Rijswijk, The Netherlands.
Wynford-Thomas, D. &Williams, E. D. (1986) Use of bromodeoxyuridine for cell kinetic studies in intact animals.Cell Tissue Kinet. 19, 179–82.
Yokoi, Y., Namihisa, T., Kuroda, H., Komatsu, I., Miyazaki, A., Watanabe, S. &Usui, K. (1984) Immunocytochemical detection of desmin in fat-storing cells (Ito cells).Hepatology 4, 709–14.
Yokoi, Y., Namihisa, T., Matsuzaki, K., Miyazaki, A. &Yamaguchi, Y. (1988) Distribution of Ito cells in experimental hepatic fibrosis.Liver 8, 48–52.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Johnson, S.J., Hines, J.E. & Burt, A.D. Immunolocalization of proliferating perisinusoidal cells in rat liver. Histochem J 24, 67–72 (1992). https://doi.org/10.1007/BF01082441
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01082441