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Cellular reorganisation of membrane peptidases in Wallerian degeneration of pig peripheral nerve

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Journal of Neurocytology

Summary

Immunohistochemical techniques have been used to study a group of membrane peptidases in the distal segment of the ulnar nerve of piglets 7 and 14 days after surgical section. Five peptidases were studied, all of which have a wide distribution on the surfaces of many cell types and have roles in metabolising neuropeptides. In normal pig nerves, endopeptidase-24.11 is expressed by both myelin- and nonmyelin-forming Schwann cells. Peptidyl dipeptidase A (angiotensin converting enzyme), aminopeptidase-N and dipeptidyl peptidase IV are present in the microvessels, and aminopeptidase-N is also seen in the perineurial connective tissue. Of this group of peptidases, only aminopeptidase-W is a neuronal marker in normal nerve. Macrophages were identified by two antibodies, 74-22-15 and 40D (which recognises Ia). Short-term cultures of macrophages obtained by alveolar lavage were positively stained by both antibodies and about half of the cells also expressed aminopeptidase-N and dipeptidyl peptidase IV. Staining by 40D and 74-22-15 revealed the presence of significant numbers of macrophages in normal nerve, but none of the membrane peptidases colocalized with these cells. Seven days after section of the nerve, the distal segment showed morphological changes typical of Wallerian degeneration. Endopeptidase-24.11 was no longer visible in myelin sheaths, but remained a marker for the surface of Schwann cells (defined also by staining for glial fibrillary acidic protein). The macrophage markers revealed marked changes in the morphology of these cells, often consistent with their phagocytic activity. Two peptidases, aminopeptidase-N and aminopeptidase-W, also appeared at this time to be associated with cells exhibiting the morphology of activated macrophages. This association could be confirmed in many instances by double staining with 74-22-15 and antibodies to the peptidases. Angiotensin converting enzyme retained its single location in microvessels at 7 days after section, but at 14 days a new pattern emerged as it, too, was expressed by macrophages. Dipeptidyl peptidase IV was not shown to be a macrophage marker in the degenerating nerve. Thus Wallerian degeneration leads to remarkable changes in the cellular expression of membrane peptidases; endopeptidase-24.11 reflects the changed morphology of Schwann cells while aminopeptidase-N, aminopeptidase-W and angiotensin converting enzyme become expressed by the actively phagocytosing macrophages.

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References

  • Abercrombie, M. &Johnson, M. L. (1946) Quantitative histology of Wallerian degeneration: 1 nuclear population in rabbit sciatic nerve.Journal of Anatomy 80, 37–56.

    Google Scholar 

  • Adams, D. O. &Hamilton, T. A. (1984) The cell biology of macrophage activation.Annual Review of Immunology 2, 283–318.

    PubMed  Google Scholar 

  • Allt, G. (1976) Pathology of the peripheral nerve. InThe Peripheral Nerve (edited byLandon, D. N.) pp. 703–16. London: Chapman and Hall.

    Google Scholar 

  • Barnes, K., Matsas, R., Hooper, N. M., Turner, A. J. &Kenny, A. J. (1988a) Endopeptidase-24.11 is striosomally ordered in pig brain, and in contrast to aminopeptidase N and peptidyl dipeptidase A (‘angiotensin converting enzyme’) is a marker for a set of striatal efferent fibres.Neuroscience 27, 799–817.

    PubMed  Google Scholar 

  • Barnes, K., Turner, A. J. &Kenny, A. J. (1988b) Electronmicroscopic immunocytochemistry of pig brain shows that endopeptidase-24.11 is localized in neuronal membranes.Neuroscience Letters 94, 64–9.

    PubMed  Google Scholar 

  • Barnes, K., Bourne, A., Cook, P. A., Turner, A. J. &Kenny, A. J. (1991) Membrane peptidases in the peripheral nervous system of the pig: their localization by immunohistochemistry at light and electron microscopic levels.Neuroscience 44, 245–61.

    PubMed  Google Scholar 

  • Beuche, W. &Friede, R. L. (1984) The role of non-resident cells in Wallerian degeneration.Journal of Neurocytology 13, 767–96.

    Google Scholar 

  • Bonnekoh, P. G. H., Scheidt, P. &Friede, R. (1989) Myelin phagocytosis by peritoneal macrophages in organ cultures of mouse peripheral nerve. A new model for studying myelin phagocytosisin vitro.Journal of Neuropathology & Experimental Neurology 48, 140–53.

    Google Scholar 

  • Bourne, A. &Kenny, A. J. (1990) The hydrolysis of brain and atrial natriuretic peptides by porcine choroid plexus membranes is attributable to endopeptidase-24.11.Biochemical Journal 271, 381–5.

    PubMed  Google Scholar 

  • Bourne, A., Barnes, K., Taylor, B. A., Turner, A. J. &Kenny, A. J. (1989) Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid.Biochemical Journal 259, 69–80.

    PubMed  Google Scholar 

  • Bowes, M. A. &Kenny, A. J. (1987) An immunohistochemical study of endopeptidase-24.11 and aminopeptidase-N in lymphoid tissues.Immunology 60, 247–53.

    PubMed  Google Scholar 

  • Bunge, M. B., Bunge, R. P., Kleitman, N. &Dean, A. C. (1989) Role of peripheral nerve extracellular matrix in Schwann cell function and neurite regeneration.Developmental Neuroscience 11, 348–60.

    PubMed  Google Scholar 

  • Chantry, A. &Glynn, P. (1990) A novel proteinase originally isolated from brain myelin is present in many tissues.Biochemical Journal 268, 245–8.

    PubMed  Google Scholar 

  • Chantry, A., Earl, C., Groome, N. &Glynn, P. (1988) Metalloendoprotease cleavage of 18.2- and 14.1-kilodalton basic proteins dissociating from rodent myelin membranes generates 10.0- and 5.9-kilodalton C-terminal fragments.Journal of Neurochemistry 50, 688–94.

    PubMed  Google Scholar 

  • Clemence, A., Mirsky, R. &Jessen, K. R. (1989) Nonmyelin-forming Schwann cells proliferate rapidly during Wallerian degeneration in the rat sciatic nerve.Journal of Neurocytology 18, 185–92.

    PubMed  Google Scholar 

  • Fawcett, J. W. &Keynes, R. J. (1990) Peripheral nerve regeneration.Annual Reviews of Neuroscience 13, 43–60.

    Google Scholar 

  • Friedland, J., Setton, C. &Silverstein, E. (1977) Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture.Science 197, 64–5.

    PubMed  Google Scholar 

  • Gee, N. S., Bowes, M. A., Buck, P. &Kenny, A. J. (1985) An immunoradiometric assay for endopeptidase-24.11 shows it to be a widely distributed enzyme in pig tissues.Biochemical Journal 228, 119–126.

    PubMed  Google Scholar 

  • Hinman, L. M., Stevens, C., Matthay, R. A. &Gee, J. B. L. (1979) Angiotensin convertase activities in human alveolar macrophages: effects of cigarette smoking and sarcoidosis.Science 205, 202–3.

    PubMed  Google Scholar 

  • Hooper, N. M., Kenny, A. J. &Turner, A. J. (1985) The metabolism of neuropeptides. Neurokinin A (substance K) is a substrate for endopeptidase-24.11 but not for peptidyl dipeptidase A (angiotensin-converting enzyme).Biochemical Journal 231, 357–61.

    PubMed  Google Scholar 

  • Jessen, I. R., Morgan, L., Stewart, H. J. S. &Mirsky, R. (1990) Three markers of adult non-myelin-forming Schwann cells, 217c(RAN-1), A5E3 and GFAP: development and regulation by neuron-Schwann cell interactions.Development 109, 91–103.

    PubMed  Google Scholar 

  • Kenny, A. J., Stephenson, S. L. &Turner, A. J. (1987) Cell surface peptidases. InMammalian Ectoenzymes (edited byKenny, A. J. &Turner, A. J.) pp. 169–210. Amsterdam: Elsevier.

    Google Scholar 

  • Kromer, L. F. &Cornbrooks, C. J. (1985) Transplants of Schwann cell cultures promote axonal regrowth in the adult mammalian brain.Proceedings of the National Academy of Sciences (USA) 82, 6330–4.

    Google Scholar 

  • Lunney, J. K. &Pescovitz, M. D. (1988) Differentiation antigens of swine lymphoid tissues. InDifferentiation Antigens in Lymphohemopoietic Tissues (edited byMiyasaka, M. &Trnka, Z.) pp. 421–53. New York & Basle: Marcel Dekker Inc.

    Google Scholar 

  • Matsas, R. &Kenny, A. J. (1989) Immunocytochemical localization of endopeptidase-24.11 in cultured neurons from pig striatum.Neuroscience 31, 237–46.

    PubMed  Google Scholar 

  • Matsas, R., Fulcher, I. S., Kenny, A. J. &Turner, A. J. (1983) Substance P and [Leu]enkephalin are hydrolyzed by an enzyme in pig caudate synaptic membranes that is identical with the endopeptidase of kidney microvilli.Proceedings of the National Academy of Sciences (USA) 80, 3111–15.

    Google Scholar 

  • Matsas, R., Kenny, A. J. &Turner, A. J. (1984) The metabolism of neuropeptides. The hydrolysis of peptides, including enkephalins, tachykinins and their analogues, by endopeptidase-24.11.Biochemical Journal 223, 433–40.

    PubMed  Google Scholar 

  • Matsas, R., Kenny, A. J. &Turner, A. J. (1986) An immunohistochemical study of endopeptidase-24.11 (‘enkephalinase’) in the pig nervous system.Neuroscience 18, 991–1012.

    PubMed  Google Scholar 

  • Oldfors, A. (1980) Macrophages in peripheral nerves. An ultrastructural and enzyme histochemical study on rats.Acta Neuropathologica 49, 43–9.

    PubMed  Google Scholar 

  • Pierart, M. E., Najovski, T., Appleboom, T. E. &Deschodt-Lanckmann, M. M. (1988) Effect of Human Endopeptidase-24.11 (‘Enkephalinase’) on IL-1-induced thymocyte proliferation activity.Journal of Immunology 140, 3808–11.

    Google Scholar 

  • Romine, J. S., Bray, G. M. &Aguayo, A. J. (1976) Schwann cell multiplication after crush injury of unmyelinated fibers.Archives of Neurology 33, 49–54.

    PubMed  Google Scholar 

  • Schubert, T. &Friede, R. L. (1981) The role of endoneurial fibroblasts in myelin degradation.Journal of Neuropathology and Experimental Neurology 40, 134–54.

    PubMed  Google Scholar 

  • Schwartz, M., Cohen, A., Stein-Izsak, C. &Belkin, M. (1989) Dichotomy of the glial response to axonal injury and regeneration.FASEB Journal 3, 2371–8.

    PubMed  Google Scholar 

  • Stephenson, S. L. &Kenny, A. J. (1987a) Metabolism of neuropeptides. Hydrolysis of the angiotensins, bradykinin, substance P and oxytocin by pig kidney microvillar membranes.Biochemical Journal 241, 237–47.

    PubMed  Google Scholar 

  • Stephenson, S. L. &Kenny, A. J. (1987b) The hydrolysis of α-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase-24.11.Biochemical Journal 243, 183–7.

    PubMed  Google Scholar 

  • Stoll, G., Griffin, J. W., Li, C. Y. &Trapp, B. D. (1989a) Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation.Journal of Neurocytology 18, 671–83.

    Google Scholar 

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Authors and Affiliations

  1. Membrane Peptidase Research Group, Department of Biochemistry & Molecular Biology, University of Leeds, LS2 9JT, Leeds, UK

    A. J. Kenny & A. Bourne

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  1. A. J. Kenny
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  2. A. Bourne
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Kenny, A.J., Bourne, A. Cellular reorganisation of membrane peptidases in Wallerian degeneration of pig peripheral nerve. J Neurocytol 20, 875–885 (1991). https://doi.org/10.1007/BF01190466

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  • DOI: https://doi.org/10.1007/BF01190466

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