Skip to main content
Log in

The role of non-resident cells in Wallerian degeneration

  • Published:
Journal of Neurocytology

Summary

Wallerian degeneration was studied in the phrenic or sciatic nerves of mice following transplantation into Millipore diffusion chambers of 0.22 μm pore size which were implanted in the peritoneal cavity and kept for up to eight weeks. This method positively eliminates the access of nonresident cells to the tissue, at the same time providing proper conditions for tissue survival. Such nerves showed no proliferation of Schwann cells and no evidence for their active role in the removal or digestion of myelin. Schwann cells rejected their sheaths and the latter persisted for weeks, leading either to sheath distension (the sheath becoming wider and thinner) or to collapse (the sheath becoming thicker, collapsing upon the empty axis cylinder). The outer envelope of Schwann cytoplasm separated into pseudopodia rich in microtubules. Sheath rejection led to a slow decay of the myelin in the absence of active phagocytosis. There was profuse fibroblastic proliferation from the epineurium and perineurium, from which cells migrated into the chambers developing fatty change. No evidence was found to link the fatty change in fibroblasts to sheath decay.

Diffusion chambers of 5.0 μm pore size were invaded by leukocytes and monocytes. Nerves kept in such chambers showed active phagocytosis of myelin leading to its removal, similar to Wallerian degenerationin situ. Phagocytes were shown to attack selectively the rejected myelin sheaths, distinguishing the latter from the surviving Schwann cells, even though both structures derive from the same cell.

The activity of phagocytes in digesting myelin was mediated by a signal which diminished in intensity with time; there was very little active phagocytosis of myelin in nerves that had been predegenerated in 0.22 μm pore chambers. Various modifications of the experiment, including studies with co-cultured peritoneal macrophages or bone marrow, indicate a need for additional activating factors to induce myelin phagocytosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abercrombie, M. &Johnson, M. L. (1942) The outwandering of cells in tissue cultures of nerves undergoing Wallerian degeneration.Journal of Experimental Biology 19, 266–83.

    Google Scholar 

  • Abercrombie, M. &Johnson, M. L. (1946) Quantitative histology of Wallerian degeneration. I. Nuclear population in rabbit sciatic nerve.Journal of Anatomy 80, 37–50.

    Google Scholar 

  • Adams, D. O., Edelson, P. J. &Koren, H. S. (1981)Methods for Studying Mononuclear Phagocytes. New York, London: Academic Press.

    Google Scholar 

  • Asbury, A. K. (1967) Schwann cell proliferation in developing mouse sciatic nerve. A radioautographic study.Journal of Cell Biology 34, 735–43.

    PubMed  Google Scholar 

  • Asbury, A. K. (1970) The histogenesis of phagocytes during Wallerian degeneration: radioautographic observations. InProceedings of the VIth International Congress of Neuropathology, pp. 666–82. Paris: Masson.

    Google Scholar 

  • Asbury, A. K. (1975) The biology of Schwann cells. InPeripheral Neuropathy, Vol. 1 (edited byDyck, P. J., Thomas, P. K. andLambert, E. H.), pp. 201–12. Philadelphia: Saunders.

    Google Scholar 

  • Benestad, H. B. (1970) Formation of granulocytes and macrophages in diffusion chamber cultures of mouse blood leucocytes.Scandinavian Journal of Haematology 7, 279–88.

    PubMed  Google Scholar 

  • Berman, I. &Kaplan, H. S. (1959) The cultivation of mouse bone marrowin vivo.Blood 14, 1040–6.

    PubMed  Google Scholar 

  • Bignami, A., Dahl, D., Nguyen, B. T. &Crosby, C. J. (1981) The fate of axonal debris in Wallerian degeneration of rat optic and sciatic nerves.Journal of Neuropathology and Experimental Neurology 40, 537–50.

    PubMed  Google Scholar 

  • Blok, J., Underwater, J. J. M., De Water, R. &Ginsel, L. A. (1982) A cytochemical method for the demonstration of 5′-nucleotidase in mouse peritoneal macrophages, with cerium ions used as trapping agent.Histochemistry 75, 437–43.

    PubMed  Google Scholar 

  • Blümcke, S. &Niedorf, H. R. (1966) Electron microscope studies of Schwann cells during the Wallerian degeneration with special reference to the cytoplasmic filaments.Acta neuropathologica 6, 46–60.

    PubMed  Google Scholar 

  • Bunge, M. B., Williams, A. K. &Wood, P. M. (1982) Neuron-Schwann cell interaction in basal lamina formation.Developmental Biology 92, 449–60.

    PubMed  Google Scholar 

  • Cajal, S.Y Ramon (1928)Degeneration and Regeneration of the Nervous System, Vol. 1. New York: Hafner Publ. Co. (reprinted 1959).

    Google Scholar 

  • Causey, G. (1960)The Cell of Schwann. Edinburgh, London: Livingstone.

    Google Scholar 

  • Cohn, Z. A. &Benson, B. (1965) The differentiation of mononuclear phagocytes. Morphology, cytochemistry, and biochemistry.Journal of Experimental Medicine 121, 153–70.

    PubMed  Google Scholar 

  • Cravioto, H. (1969) The ultrastructure of acoustic nerve tumors.Acta neuropathologica 12, 116–40.

    PubMed  Google Scholar 

  • Daems, W. T. &Brederoo, P. (1973) Electron microscopical studies on the structure, phagocytic properties, and peroxidatic activity of resident and exudate peritoneal macrophages in the guinea pig.Cell and Tissue Research 144, 247–97.

    PubMed  Google Scholar 

  • Daems, W. T. &Koerten, H. K. (1978) The effects of various stimuli on the cellular composition on peritoneal exudates in the mouse.Cell and Tissue Research 190, 47–60.

    PubMed  Google Scholar 

  • Daems, W. T., Poelmann, R. E. &Brederoo, P. (1973) Peroxidatic activity in resident peritoneal macrophages and exudate monocytes of the guinea pig after ingestion of latex particles.Journal of Histochemistry and Cytochemistry 21, 93–5.

    PubMed  Google Scholar 

  • Epstein, L. G., Prineas, J. W. &Raine, C. S. (1983) Attachment of myelin to coated pits on macrophages in experimental allergic encephalomyelitis.Journal of the Neurological Sciences 61, 341–8.

    PubMed  Google Scholar 

  • Friede, R. L. &Johnstone, M. A. (1967) Responses of thymidine labeling of nuclei in gray matter and nerve following sciatic transection.Acta neuropathologica 7, 218–31.

    PubMed  Google Scholar 

  • Friede, R. L. &Martinez, A. J. (1970a) Analysis of the process of sheath expansion in swollen nerve fibers.Brain Research 19, 165–82.

    PubMed  Google Scholar 

  • Friede, R. L. &Martinez, A. J. (1970b) Analysis of axon-sheath relations during early Wallerian degeneration.Brain Research 19, 199–212.

    PubMed  Google Scholar 

  • Friede, R. L. &Miyagishi, T. (1972) Adjustment of the myelin sheath to changes in axon caliber.Anatomical Record 172, 1–13.

    PubMed  Google Scholar 

  • Friede, R. L. &Samorajski, T. (1968) Myelin formation in the sciatic nerve of the rat. A quantitative electron microscopic, histochemical and radioautographic study.Journal of Neuropathology and Experimental Neurology 27, 546–70.

    PubMed  Google Scholar 

  • Gibson, J. D. (1979) The origin of the neural macrophage: a quantitative ultrastructural study of cell population changes during Wallerian degeneration.Journal of Anatomy 129, 1–19.

    PubMed  Google Scholar 

  • Goldstein, J. L., Anderson, R. G. W. &Brown, M. S. (1979) Coated pits, coated vesicles, and receptor-mediated endocytosis.Nature 279, 679–85.

    PubMed  Google Scholar 

  • Guth, L. (1956) Regeneration in the mammalian peripheral nervous system.Physiological Reviews 36, 441–78.

    PubMed  Google Scholar 

  • Hall, S. M. (1978) The Schwann cell: A reappraisal of its role in the peripheral nervous system.Neuropathology and Applied Neurobiology 4, 165–76.

    PubMed  Google Scholar 

  • Joseph, J. (1950) Further studies in changes of nuclear population in degenerating non-myelinated and finely myelinated nerves.Acta anatomica 9, 279–88.

    Google Scholar 

  • Lampert, P. W. &Cressman, M. R. (1966) Fine-structural changes of myelin sheaths after axonal degeneration in the spinal cord of rats.American Journal of Pathology 49, 1139–55.

    PubMed  Google Scholar 

  • Lampert, P. W. &Schochet, Jr, S. S. (1968) Demyelination and remyelination in lead neuropathy.Journal of Neuropathology and Experimental Neurology 27, 527–45.

    PubMed  Google Scholar 

  • Leblond, C. P., Messier, B. &Kopriwa, B. (1959) Thymidine-H3 as a tool for the investigation of the renewal of cell populations.Laboratory Investigation 8, 296–308.

    PubMed  Google Scholar 

  • Leibovich, S. J. (1978) Production of macrophage-dependent fibroblast-stimulating activity (M-FSA) by murine macrophages. Effects on BALBc 3T3 fibroblasts.Experimental Cell Research 113, 47–56.

    PubMed  Google Scholar 

  • Leibovich, S. J. &Ross, R. (1976) A macrophage-dependent factor that stimulates the proliferation of fibroblastsin vitro.American Journal of Pathology 84, 501–13.

    PubMed  Google Scholar 

  • Ling, E. A. (1978) Electron microscopic studies of macrophages in Wallerian degeneration of rat optic nerve after intravenous injection of colloidal carbon.Journal of Anatomy 126, 111–21.

    PubMed  Google Scholar 

  • Ling, E. A. (1979) Evidence for a haematogenous origin of some of the macrophages appearing in the spinal cord of the rat after dorsal rhizotomy.Journal of Anatomy 128, 143–54.

    PubMed  Google Scholar 

  • Liu, H. M. (1973) Schwann cell properties: 1. Origin of Schwann cell during peripheral nerve regeneration.Journal of Neuropathology and Experimental Neurology 32, 458–73.

    PubMed  Google Scholar 

  • Liu, H. M. (1974) Schwann cell properties. II. The identity of phagocytes in the degenerating nerve.American Journal of Pathology 75, 395–405.

    PubMed  Google Scholar 

  • Luse, S. (1968) The Schwann cell. InPathology of the Nervous System (edited byMinckler, J.), pp. 585–607. New York: McGraw-Hill Book Co.

    Google Scholar 

  • Mustafa, G. Y. &Gamble, H. J. (1978) Observations on the development of the connective tissues of developing human nerve.Journal of Anatomy 127, 141–55.

    PubMed  Google Scholar 

  • Nageotte, J. (1932) Sheaths of the peripheral nerves. Nerve degeneration and regeneration. InCytology and Cellular Pathology of the Nervous System, Vol. 1 (edited byPenfield, W.), pp. 191–239. New York: Hoeber.

    Google Scholar 

  • Nathaniel, E. J. H. &Pease, D. C. (1963) Degenerative changes in rat dorsal roots during Wallerian degeneration.Journal of Ultrastructure Research 9, 511–32.

    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 

  • Olsson, Y. &Sjöstrand, J. (1969) Origin of macrophages in Wallerian degeneration of peripheral nerves demonstrated autoradiographically.Experimental Neurology 23, 102–12.

    PubMed  Google Scholar 

  • Parwaresch, M. R., Radzun, H. J. &Dommes, M. (1981) The homogeneity and monocytic origin of human peritoneal macrophages evidenced by comparison of esterase polymorphism.American Journal of Pathology 102, 209–18.

    PubMed  Google Scholar 

  • Peyronnard, J. -M., Aguayo, A. J. &Bray, G. M. (1973) Schwann cell internuclear distances in normal and regenerating unmyelinated nerve fibers.Archives of Neurology 29, 56–9.

    PubMed  Google Scholar 

  • Ranvier, L. (1878)Leçons sur l'Histologie du Système Nerveux. Paris: Savy.

    Google Scholar 

  • Rastogi, S. C. &Clausen, J. (1981) Degradation of basic protein and Wolfgram protein in central nervous system myelin by soluble enzymes of human peripheral polymorphonuclear leucocytes.Journal of the Neurological Sciences 51, 161–9.

    PubMed  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 

  • Salzer, J. L. &Bunge, R. P. (1980) Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury.Journal of Cell Biology 84, 739–52.

    PubMed  Google Scholar 

  • Satinsky, D., Pepe, F. A. &Liu, C. N. (1964) The neurilemma cell in peripheral nerve degeneration and regeneration.Experimental Neurology 9, 441–51.

    Google Scholar 

  • Schlaepfer, W. W. &Hager, H. (1964) Ultrastructural studies of INH-induced neuropathy in rats. II. Alteration and decomposition of the myelin sheath.American Journal of Pathology 45, 423–30.

    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., Sela, B. A. &Eshhar, N. (1982) Antibodies to gangliosides and myelin autoantigens are produced in mice following sciatic nerve injury.Journal of Neurochemistry 38, 1192–5.

    PubMed  Google Scholar 

  • Shuman, S., Hardy, M. &Pleasure, D. (1983) Peripheral nervous system myelin and Schwann cell glycoproteins: identification by lectin binding and partial purification of a peripheral nervous system myelin-specific 170 000 molecular weight glycoprotein.Journal of Neurochemistry 41, 1277–85.

    PubMed  Google Scholar 

  • Speidel, C. C. (1935) Studies on living nerves. III. Phenomena of nerve irritation and recovery, degeneration and repair.Journal of Comparative Neurology 61, 1–83.

    Google Scholar 

  • Volkman, A. (1976) Monocyte kinetics and their changes in infection. InImmunobiology of the Macrophage (edited byNelson, D. S.), pp. 291–322. New York, London: Academic Press.

    Google Scholar 

  • Volkman, A., Chang, N. C., Strausbauch, P. H. &Morahan, P. S. (1983) Differential effects of chronic monocyte depletion on macrophage populations.Laboratory Investigation 49, 291–8.

    PubMed  Google Scholar 

  • Wechsler, W. &Hager, H. (1962) Elektronenmikroskopische Untersuchung der Wallerschen Degeneration des peripheren Säugetiernerven.Beiträge zur pathologischen Anatomie und zur allgemeinen Pathologie 126, 352–80.

    Google Scholar 

  • Weiss, P. &Wang, H. (1945) Transformation of adult Schwann cells into macrophages.Proceedings of the Society for Experimental Biology and Medicine 58, 273–5.

    Google Scholar 

  • Were, Z. (1983) How the macrophage regulates its extracellular environment.American Journal of Anatomy 166, 237–56.

    PubMed  Google Scholar 

  • Wisniewski, H., Prineas, J. &Raine, C. S. (1969) An ultrastructural study of experimental demyelination and remyelination.Laboratory Investigation 21, 105–18.

    PubMed  Google Scholar 

  • Young, J. Z. (1945) The history of the shape of a nerve fibre. InEssays on Growth and Form, Presented toD'Arcy Wentworth Thompson (edited byLegros Clark, W. E. andMedawar, P. B.), pp. 41–94. Oxford: Clarendon Press.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beuche, W., Friede, R.L. The role of non-resident cells in Wallerian degeneration. J Neurocytol 13, 767–796 (1984). https://doi.org/10.1007/BF01148493

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01148493

Keywords

Navigation