Human IgM anti-GM1 autoantibodies modulate intracellular calcium homeostasis in neuroblastoma cells

Angelo Quattrini, Isabella Lorenzetti, Clara Sciorati, Massimo Corbo, Stefano C. Previtali, M. Laura Feltri, Nicola Canal, Lawrence Wrabetz, Raffaello Nemni, Emilio Clementi

Research output: Contribution to journalArticlepeer-review

Abstract

Increased titers of IgM anti-GM1 antibodies are present in some patients with Lower Motor Neuron Disease (LMND) or Motor Neuropathy (MN), but their pathogenic role and the mechanism of action are unclear. Previous studies have shown that the B subunit of Cholera Toxin (CT), which binds and crosslinks ganglioside GM1, modulate intracellular calcium in murine neuroblastoma cells via the activation of L-type voltage-dependent calcium channels (VGCC). Therefore, using a fluorimetric approach, we have examined the hypothesis that the pentameric IgM anti-GM1 antibodies, could similarly alter calcium concentration in N18 neuroblastoma cells. Sera with human IgM anti-GM1 antibodies were obtained from 5 patients with LMND and 2 patients with MN. Human IgG anti-GM1, IgM anti-Myelin Associated Glycoprotein (MAG), IgM anti-sulfatide antibodies and lectin peanut agglutinin (PNA), that recognizes specifically the Gal(βl-3)GalNAc epitope, were used as control sera. Direct application of either human IgM anti-GM1 antibodies or the B subunit of CT to N18 neuroblastoma cells induced a sustained influx of manganese ions, as indicated by a quench of the intracellular fura-2 fluorescence. Furthermore, the dihydropyridine L-type channel antagonists completely inhibited the manganese influx, suggesting that it is due to activation of an L-type VGCC. The magnitude of the influx was correlated with antibody titers. None of human IgG anti-GM1, IgM anti-MAG, IgM anti-sulfatide antibodies or PNA induce an ion influx, pointing to the selective participation of the pentameric IgM isotype of anti-GM1 in the modulation of L-type calcium channels opening. Given that L-type calcium channels are present on motor neurons, the modulation of L-type calcium channels by IgM GM1 antisera may have important implications in diseases such as LMND and MN.

Original languageEnglish
Pages (from-to)213-219
Number of pages7
JournalJournal of Neuroimmunology
Volume114
Issue number1-2
DOIs
Publication statusPublished - Mar 1 2001

Keywords

  • Calcium Channel
  • Cholera Toxin
  • Gangliosides
  • Lower Motor Neuron Disease
  • Motor Neuropathy

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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