Macrophage apolipoprotein synthesis and endoneurial distribution as a response to segmental demyelination

Benjamin B. Gelman, Jeffry Goodrum, Thomas W. Bouldin

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The synthesis and endoneurial distribution of apolipoproteins in response to myelin degradation was elucidated morphologically and biochemically in rodent models of segmental demyelination. At the onset of acute demyelination induced by tellurium (Te) poisoning, macrophages infiltrated the endoneurium and then began to express cytoplasmic immunoreactivity for apolipoprotein E (apo E). When de-myelinating nerve slices were incubated with S3 5-methionine, radiolabeled apo E was released, showing that apo E was actively synthesized by the macrophages. Macrophages secreted apo E into the endoneurial spaces, leading to dense endoneurial accumulations. Other apolipoproteins (apo A1 and albumin) were not synthesized in the endoneurium, but they entered edematous nerves, presumably through an early breakdown in the blood-nerve barrier. During the phagocytosis of myelin, plasma-derived apolipoproteins accumulated within some of the macrophages. In chronic demyelination caused by lead poisoning, the cellular and extracellular distribution of apolipoproteins was similar to Te neuropathy; the amount of apo E accumulation and the macrophage density were proportional to the prevalence of active demyelination in teased fibers. Similar patterns of endoneurial apo E were present in an inherited form of demyelination in the twitcher mouse, after antibody-mediated demyelination, and in demyelination secondary to axonal degeneration. Human sural nerve biopsies had patterns of apolipoprotein E antigenicity that were comparable to the rodent models. We conclude that secretion of apo E by infiltrating macrophages is a generalized response to demyelination, and that endoneurial edema leads to the accumulation of certain plasma apolipoproteins within macrophages. These data suggest that endoneurial apolipoproteins and macrophages might mediate important functions in patients recovering from primary and secondary demyelination.

Original languageEnglish (US)
Pages (from-to)383-407
Number of pages25
JournalJournal of Neuropathology and Experimental Neurology
Volume50
Issue number4
DOIs
StatePublished - Jul 1991

Keywords

  • Apolipoprotein E
  • Endoneurial edema
  • Macrophage
  • Segmental demyelination
  • Tellurium neuropathy
  • Twitcher mouse
  • Wallerian degeneration

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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