Research paper
Complement depletion affects demyelination and inflammation in experimental allergic neuritis

https://doi.org/10.1016/0165-5728(95)00006-NGet rights and content

Abstract

The effect of systemic complement depletion by cobra venom factor (CVF) on experimental allergic neuritis (BAN) was studied in rats immunized with variable amounts of bovine peripheral nerve myelin. Low-dose myelin EAN rats treated with CVF i.p. (n = 10) had lower clinical scores (0.3 ± 0.7 vs. 1.1 ± 1.1), less demyelination (0.4 ± 0.8 vs. 1.9 ± 1.1) and inflammation (0.6 ± 1.2 vs. 2 ± 1) than EAN animals treated with i.p. saline (n = 10). Endoneurial infiltrates had fewer EDI-positive (phagocytic) macrophages (if0.4 ± 0.5 vs.> 1.6 ± 1.1) and CD11bc-positive (expressing iC3b receptor or CR3) cells (1 ± 0.8 vs. 2.5 ± 0.8) (mean ± S.D.) detected by immunocytochemistry. This effect was partially abrogated by immunizing animals with a higher dose of myelin. Our studies suggest that complement may play a role in the recruitment of macrophages into the endoneurium and in opsonizing myelin for phagocytosis.

References (37)

  • J.W. Griffin et al.

    Macrophage systems in peripheral nerves. A review

    J. Neuropathol. Exp. Neurol.

    (1993)
  • A.F. Hahn et al.

    Passive transfer of demyelination by experimental allergic neuritis serum

    Acta Neuropathol.

    (1980)
  • A.F. Hahn et al.

    Demyelination and axonal degeneration in Lewis rat experimental allergic neuritis depend on the myelin dosage

    Lab. Invest.

    (1988)
  • A.F. Hahn et al.

    P2- peptide induced experimental allergic neuritis: a model to study axonal degeneration

    Acta Neuropathol.

    (1991)
  • H.P. Hartung et al.

    The role of macrophages and eicosanoids in the pathogenesis of experimental allergic neuritis. Serial clinical, electrophysiological, biochemical and morphological observations

    Brain

    (1988)
  • H.P. Hartung et al.

    T cell activation in Guilain-Barré syndrome and in MS: Elevated serum levels of soluble IL-2 receptors

    Neurology

    (1990)
  • H.P. Hartung et al.

    Serum interleukin-2 concentrations in Guillain-Barre syndromeand chronic idiopathic demyelinating polyradiculoneuropathy: comparison with other neurological diseases of presumed immunopathogenesis

    Ann. Neurol.

    (1991)
  • I. Huitinga et al.

    Treatment with anti-CR3 antibodies ED7 and ED8 suppresses experimental allergic encephalomyelitis in Lewis rats

    Eur. J. Immunol.

    (1993)
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    Presented at the Peripheral Nerve Society meeting, Minneapolis, June 1994.

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