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Scand J Immunol. 2007 Aug-Sep;66(2-3):345-51.

CD59 efficiently protects human NT2-N neurons against complement-mediated damage.

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1
Institute of Immunology, Rikshospitalet HF, University of Oslo, Oslo, Norway. pedersen@medisin.uio.no

Abstract

The complement regulatory protein CD59 controls cell survival by the inhibition of C5b-9 formation on the cell membrane. Loss of CD59 increases the susceptibility of cells to complement-mediated damage and lysis. Deposition of IgM can induce complement activation with subsequent cell death. We have previously demonstrated the presence of CD59 on human NT2-N neurons. In this study, we investigated the functional role of CD59 for NT2-N cell survival after IgM-mediated complement activation. Complement activation was induced on NT2-N neurons with human serum following incubation with the IgM monoclonal antibody A2B5 reacting with a neuronal cell membrane epitope. Deposition of C1q and C5b-9 was detected on the cell membrane and sC5b-9 in the culture supernatant. Specific inhibition of complement was obtained by the C3 inhibitor compstatin, and by anti-C5/C5a MoAb. CD59 was blocked by the MoAb BRIC 229. Membrane damage of propidium iodide-stained NT2-N cells was confirmed by immunofluorescence microscopy and degeneration of neuronal processes was shown with crystal violet staining. A2B5, but not the irrelevant control IgM antibody, induced complement activation on NT2-N neurons after incubation with a human serum, as detected by the deposition of C1q. A marked membrane deposition of C5b-9 on NT2-N neurons with accompanying cell death and axonal degeneration was found after the blocking of CD59 with MoAb BRIC 229 but not with an isotype-matched control antibody. Compstatin and anti-C5 monoclonal antibodies which blocked C5 activation efficiently inhibited complement activation. In conclusion, CD59 is essential for protecting human NT2-N neurons against complement-mediated damage, which is known to occur in a number of clinical conditions including stroke.

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