Antiphospholipid antibodies bind to rat cerebellar granule cells: the role of N-methyl-D-aspartate receptors.
IgGs from sera containing antiphospholipid antibodies (aPL), detected as antibodies to cardiolipin, or control sera were incubated with rat cerebellar granule cells in primary culture. Using a mitochondrial dehydrogenase activity assay (MTT test), aPL IgGs were shown to decrease MTT metabolism after 24 h incubation with the cells, and to cause non-toxic amounts of glutamate to become neurotoxic when added to the cells for 45 min. Acute and chronic aPL toxicity were prevented by MK-801. Sera containing aPL bound to intact cerebellar neurons, as revealed by an immunofluorescent technique. These results suggest that antiphospholipid antibodies interfere with excitatory pathways in glutamatergic cerebellar granule cells by a mechanism involving overactivation of the NMDA glutamate receptor.
Riccio
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Institute of General Pathology, Catholic University, Rome, Italy.
Andreassi
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Eboli
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ML
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D002531:Cerebellum / Q000166:cytology / Q000276:immunology*; D004396:Coloring Agents / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008928:Mitochondria / Q000201:enzymology; D009474:Neurons / Q000276:immunology*; D009498:Neurotoxins / Q000494:pharmacology; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D004396:Coloring Agents; D018691:Excitatory Amino Acid Antagonists; D007074:Immunoglobulin G; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D013778:Tetrazolium Salts; D013844:Thiazoles; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D010088:Oxidoreductases; C022616:thiazolyl blue