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Silver stains for identification of neuroendocrine cells. A study of the chemical background

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The chemical background of silver stains used for visualization and characterization of peripheral neuroendocrine cells in the gastrointestinal tract and pancreas, and of their corresponding tumours, was studied in tissue sections and by a dot-blot technique. Sequential staining of pancreatic islets with an immunohistochemical procedure and silver staining of the same tissue section revealed that chromogranin A immunostained cells also displayed an argyrophil reaction with the Grimelius method, but no argentaffin reaction with the Masson technique. Accordingly, purified chromogranin A (15 μg or less) treated in formalin and applied to nitrocellulose did not show any argentaffin reaction but displayed a dose-related argyrophil reaction. Equal quantities of other polypeptide components did not give rise to any silver reaction. Further dot-blot studies showed that the tryptophan and tyrosine metabolites, dopamine, norepinephrine, 5-hydroxytryptamine and 5-hydroxindole caused strongly argentaffin and argyrophil reactions while epinephrine, 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophan gave only the former reaction. Among other chemical components studied, only guanine displayed weak silver staining. The results indicate that the reaction products between aldehydes and the granular content of biogenic amines synthesized from tryptophan and tryosine display an argentaffin reaction and that the granular chromogranin A caused an argyrophil but no argentaffin reaction.

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  1. Barter, R. &Pearse, A. G. E. (1953) Detection of 5-hydroxy-tryptamine in mammalian enterochromaffin cells.Nature 171, 810.

  2. Barter, R. &Pearse, A. G. E. (1953) Mammalian enterochromaffin cells as the source of serotonin (5-hydroxytryptamine).J. Path. Bact. 69, 25–31.

  3. Cohn, D. V., Zangerle, R., Fischer-Colbrie, R., Chu, L. L. H., Elting, J. J., Hamilton, J. W. &Winkler, H. (1982) Similarity of secretory protein-1 from parathyroid gland to chromogranin A from the adrenal medulla.PNAS USA 79, 6056–9.

  4. Cohn, D. V., Eltin, J. J., Frick, M. &Elde, R. (1984) Selective localization of the parathyroid secretory protein-l/adrenal medulla chromogranin A protein family in a wide variety of endocrine cells of the rat.Endocrinology 114, 1963–84.

  5. Crimelius, L. (1968) A silver nitrate stain for A2-cells of human pancreatic islets.Acta. Soc. Med. Upsal. 73, 243–70.

  6. Crimelius, L. &Wilander, E. (1980) Silver stains in the study of endocrine cells of the gut and pancreas.Invest. Cell Pathol. 3, 3–12.

  7. Grimelius, L. & Wilander, E. (1985) Silver impregnation and other non-immunocytochemical staining methods. In:Endocrine Tumours. The pathology of regulatory peptide producing tumours (eds.Polak, J. M. & Bloom, S. R.) pp. 95–115. Churchill Livingstone.

  8. Lloyd, R. V. &Wilson, B. S. (1983) Specific endocrine tissue marker defined by a monoclonal antibody.Science 222, 628–30.

  9. Lloyd, R. V., Mervak, T., Schmidt, K., Warner, T. F. C. S. &Wilson, B. S. (1984) Immunohistochemical detection of chromogranin and neuron-specific enolase in pancreatic endocrine neoplasms.Am. J. Surg. Path. 8, 607–14.

  10. Lindqvist, M. &Wilander, E. (1983) A simple procedure for immunocytochemical and silver-staining of endocrine cells in the same section.Acta Path. Microbiol. Immunol. Scand. Sect. A 91, 493–4.

  11. Lundqvist, M. &Wilander, E. (1984) Small intestinal chromaffin cells and carcinoid tumours: a study with silver stains, formalin-induced fluorescence and monoclonal antibodies to serotonin.Histochem. J. 16, 1247–56.

  12. O'Connor, D. T., Burton, D. &Deftos, L. J. (1983a) Immunoreactive human chromogranin A in diverse polypeptide hormone producing tumours and normal endocrine tissues.J. Clin. Endo. Metab. 57, 1084–6.

  13. O'Connor, D. T., Burton, D. &Deftos, L. J. (1983b) Chromogranin A: immunohistology reveals its universal occurrence in normal polypeptide hormone producing endocrine glands.Life Sciences 33, 1657–63.

  14. O'Connor, D. T., Frigon, R. P. &Sokoloff, R. L. (1984) Human chromogranin A: purification and characterization from catecholamine storage vesicles of human pheochromocytoma.Hypertension 6, 2–12.

  15. Portela-Gomes, G. M. (1982) Enterochromaffin cells. A qualitative and quantitative study.Acta Universitatis Upsaliensis. Dissertations from the Faculty of Medicine, No. 434.

  16. Rindi, G., Buffa, R., Sessa, F., Tortora, O. &Solcia, E. (1986) Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Distribution, distinction from costored hormones/prohormones and relationship with the argyrophil component of secretory granules.Histochemistry 85 (1), 19–28.

  17. Singh, I. (1964) A modification of the Masson-Hamperl method for staining of argentaffin cells.Anat. Anz. 115, 81–2.

  18. Smith, A. D., Winkler, H. (1967) Purification and properties of an acidic protein from chromaffin granules of bovine adrenal medulla.Biochem. J. 103, 483–92.

  19. Varndell, I. M., Lloyd, R. V., Wilson, B. S. &Polak, J. M. (1985) Ultrastructural localization of chromogranin: a protential marker for the electron microscopical recognition of endocrine cell secretory granules.Histochem. J. 17, 981–92.

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Correspondence to M. Lundqvist.

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Lundqvist, M., Arnberg, H., Candell, J. et al. Silver stains for identification of neuroendocrine cells. A study of the chemical background. Histochem J 22, 615–623 (1990). https://doi.org/10.1007/BF01072943

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  • Tryptophan
  • Pancreatic Islet
  • Biogenic Amine
  • Silver Staining
  • Neuroendocrine Cell